@misc{kick_grete_crisci_almond_kaeser_2023, title={Testable Candidate Immune Correlates of Protection for Porcine Reproductive and Respiratory Syndrome Virus Vaccination}, volume={11}, ISSN={["2076-393X"]}, url={https://doi.org/10.3390/vaccines11030594}, DOI={10.3390/vaccines11030594}, abstractNote={Porcine reproductive and respiratory syndrome virus (PRRSV) is an on-going problem for the worldwide pig industry. Commercial and experimental vaccinations often demonstrate reduced pathology and improved growth performance; however, specific immune correlates of protection (CoP) for PRRSV vaccination have not been quantified or even definitively postulated: proposing CoP for evaluation during vaccination and challenge studies will benefit our collective efforts towards achieving protective immunity. Applying the breadth of work on human diseases and CoP to PRRSV research, we advocate four hypotheses for peer review and evaluation as appropriate testable CoP: (i) effective class-switching to systemic IgG and mucosal IgA neutralizing antibodies is required for protective immunity; (ii) vaccination should induce virus-specific peripheral blood CD4+ T-cell proliferation and IFN-γ production with central memory and effector memory phenotypes; cytotoxic T-lymphocytes (CTL) proliferation and IFN-γ production with a CCR7- phenotype that should migrate to the lung; (iii) nursery, finishing, and adult pigs will have different CoP; (iv) neutralizing antibodies provide protection and are rather strain specific; T cells confer disease prevention/reduction and possess greater heterologous recognition. We believe proposing these four CoP for PRRSV can direct future vaccine design and improve vaccine candidate evaluation.}, number={3}, journal={VACCINES}, author={Kick, Andrew R. and Grete, Alicyn F. and Crisci, Elisa and Almond, Glen W. and Kaeser, Tobias}, year={2023}, month={Mar} }
 @article{dodkins_delaney_overton_scholle_frias_crisci_huq_jordan_kimata_goldberg_2022, title={A Rapid, High Throughput, Viral Infectivity Assay using Automated Brightfield Microscopy with Machine Learning}, volume={3}, url={https://doi.org/10.1101/2022.03.23.485512}, DOI={10.1101/2022.03.23.485512}, abstractNote={Infectivity assays are essential for the development of viral vaccines, antiviral therapies and the manufacture of biologicals. Traditionally, these assays take 2-7 days and require several manual processing steps after infection. We describe an automated assay (AVIA TM ), using machine learning (ML) and high-throughput brightfield microscopy on 96-well plates that can quantify infection phenotypes within hours, before they are manually visible, and without sample preparation. ML models were trained on HIV, influenza A virus, coronavirus 229E, vaccinia viruses, poliovirus, and adenoviruses, which together span the four major categories of virus (DNA, RNA, enveloped, and non-enveloped). A sigmoidal function, fit to virus dilution curves, yielded an R 2 higher than 0.98 and a linear dynamic range comparable to or better than conventional plaque or TCID 50 assays. Because this technology is based on sensitizing AIs to specific phenotypes of infection, it may have potential as a rapid, broad-spectrum tool for virus identification.}, publisher={Cold Spring Harbor Laboratory}, author={Dodkins, Rupert and Delaney, John R. and Overton, Tess and Scholle, Frank and Frias, Alba and Crisci, Elisa and Huq, Nafisa and Jordan, Ingo and Kimata, Jason T. and Goldberg, Ilya G.}, year={2022}, month={Mar} }
 @article{frias-de-diego_gilbertie_scholle_dejarnette_crisci_2022, title={Effect of BIO-PLYTM, a Platelet-Rich Plasma Derived Biologic on PRRSV-2-Infected Macrophages}, volume={14}, ISSN={["1999-4915"]}, url={https://doi.org/10.3390/v14122666}, DOI={10.3390/v14122666}, abstractNote={Porcine Reproductive and Respiratory Syndrome (PRRS) is the one of the most devastating diseases impacting the swine industry worldwide. Control and prevention methods rely on biosafety measures and vaccination. As an RNA virus with a high rate of mutation, vaccines are only partially effective against circulating and newly emerging strains. To reduce the burden of this disease, research on alternative control methods is needed. Here, we assess the in vitro antiviral effect of a novel platelet-rich plasma-derived biologic termed BIO-PLYTM (for the BIOactive fraction of Platelet-rich plasma LYsate) from both swine and equine origin. Our results show that BIO-PLYTM significantly reduces the amount of PRRSV viral load determined by RT-qPCR and the number of infectious viral particles measured by TCID50 in infected porcine alveolar and parenchymal macrophages. This study also showed limited toxicity of BIO-PLYTM in vitro and aspects of its immunomodulatory capacity evaluating the regulation of reactive oxygen species and cytokines production in infected cells. Finally, this study presents promising data on the effect of BIO-PLYTM on other RNA viruses such as human A influenza viruses and coronavirus.}, number={12}, journal={VIRUSES-BASEL}, author={Frias-De-Diego, Alba and Gilbertie, Jessica M. M. and Scholle, Frank and Dejarnette, Sarah and Crisci, Elisa}, year={2022}, month={Dec} }
 @article{crisci_2022, title={From Open Access to Circular Health: Ilaria Capua's Journey through Science and Politics}, volume={14}, ISSN={["1999-4915"]}, url={https://doi.org/10.3390/v14061296}, DOI={10.3390/v14061296}, abstractNote={This paper highlights the career of an exceptional woman virologist, Dr. Ilaria Capua. It recollects her major achievements, awards and noteworthy events that have shaped her scientific and political career. It retraces Dr. Capua’s major contributions to the study of viral zoonoses, in particular influenza virus, and her strong commitment to an open, more ethical science at the service of society in its broadest sense. It describes how she became the long-term champion of “Open Access” and “Data Sharing” for virus genetic sequences and introduces her new concept of “Circular Health”, where health becomes a circular system that represents a central and vital connection hub between humans and nature. This paper features Dr. Capua’s value as a role model for young women scientists and their empowerment.}, number={6}, journal={VIRUSES-BASEL}, author={Crisci, Elisa}, year={2022}, month={Jun} }
 @article{proctor_wolf_brodsky_cortes_frias-de-diego_almond_crisci_watanabe_hammer_kaeser_2022, title={Heterologous vaccine immunogenicity, efficacy, and immune correlates of protection of a modified-live virus porcine reproductive and respiratory syndrome virus vaccine}, volume={13}, ISSN={["1664-302X"]}, url={http://dx.doi.org/10.3389/fmicb.2022.977796}, DOI={10.3389/fmicb.2022.977796}, abstractNote={Although porcine reproductive and respiratory syndrome virus (PRRSV) vaccines have been available in North America for almost 30 years, many vaccines face a significant hurdle: they must provide cross-protection against the highly diverse PRRSV strains. This cross-protection, or heterologous vaccine efficacy, relies greatly on the vaccine’s ability to induce a strong immune response against various strains—heterologous immunogenicity. Thus, this study investigated vaccine efficacy and immunogenicity of a modified live virus (MLV) against four heterologous type 2 PRRSV (PRRSV-2) strains. In this study, 60 pigs were divided into 10 groups. Half were MOCK-vaccinated, and the other half vaccinated with the Prevacent ® PRRS MLV vaccine. Four weeks after vaccination, groups were challenged with either MOCK, or four PRRSV-2 strains from three different lineages—NC174 or NADC30 (both lineage 1), VR2332 (lineage 5), or NADC20 (lineage 8). Pre-and post-challenge, lung pathology, viral loads in both nasal swabs and sera, anti-PRRSV IgA/G, neutralizing antibodies, and the PRRSV-2 strain-specific T-cell response were evaluated. At necropsy, the lung samples were collected to assess viral loads, macroscopical and histopathological findings, and IgA levels in bronchoalveolar lavage. Lung lesions were only induced by NC174, NADC20, and NADC30; within these, vaccination resulted in lower gross and microscopic lung lesion scores of the NADC20 and NADC30 strains. All pigs became viremic and vaccinated pigs had decreased viremia upon challenge with NADC20, NADC30, and VR2332. Regarding vaccine immunogenicity, vaccination induced a strong systemic IgG response and boosted the post-challenge serum IgG levels for all strains. Furthermore, vaccination increased the number of animals with neutralizing antibodies against three of the four challenge strains—NADC20, NADC30, and VR2332. The heterologous T-cell response was also improved by vaccination: Not only did vaccination increase the induction of heterologous effector/memory CD4 T cells, but it also improved the heterologous CD4 and CD8 proliferative and/or IFN-γ response against all strains. Importantly, correlation analyses revealed that the (non-PRRSV strain-specific) serum IgG levels and the PRRSV strain-specific CD4 T-cell response were the best immune correlates of protection. Overall, the Prevacent elicited various degrees of efficacy and immunogenicity against four heterologous and phylogenetically distant strains of PRRSV-2.}, journal={FRONTIERS IN MICROBIOLOGY}, publisher={Frontiers Media SA}, author={Proctor, Jessica and Wolf, Iman and Brodsky, David and Cortes, Lizette M. and Frias-De-Diego, Alba and Almond, Glen W. and Crisci, Elisa and Watanabe, Tatiane Terumi Negrao and Hammer, James M. and Kaeser, Tobias}, year={2022}, month={Sep} }
 @article{pecoraro_leal_frias-de-diego_browning_odle_crisci_2022, title={The health benefits of selenium in food animals: a review}, volume={13}, ISSN={["2049-1891"]}, url={https://doi.org/10.1186/s40104-022-00706-2}, DOI={10.1186/s40104-022-00706-2}, abstractNote={Selenium is an essential trace mineral important for the maintenance of homeostasis in animals and humans. It evinces a strong antioxidant, anti-inflammatory and potential antimicrobial capacity. Selenium biological function is primarily achieved by its presence in selenoproteins as a form of selenocysteine. Selenium deficiency may result in an array of health disorders, affecting many organs and systems; to prevent this, dietary supplementation, mainly in the forms of organic (i.e., selenomethionine and selenocysteine) inorganic (i.e., selenate and selenite) sources is used. In pigs as well as other food animals, dietary selenium supplementation has been used for improving growth performance, immune function, and meat quality. A substantial body of knowledge demonstrates that dietary selenium supplementation is positively associated with overall animal health especially due to its immunomodulatory activity and protection from oxidative damage. Selenium also possesses potential antiviral activity and this is achieved by protecting immune cells against oxidative damage and decreasing viral replication. In this review we endeavor to combine established and novel knowledge on the beneficial effects of dietary selenium supplementation, its antioxidant and immunomodulatory actions, and the putative antimicrobial effect thereof. Furthermore, our review demonstrates the gaps in knowledge pertaining to the use of selenium as an antiviral, underscoring the need for further in vivo and in vitro studies, particularly in pigs.}, number={1}, journal={Journal of Animal Science and Biotechnology}, author={Pecoraro, B.M. and Leal, D.F. and Frias-De-Diego, A. and Browning, M. and Odle, J. and Crisci, E.}, year={2022}, pages={58} }
 @article{frias-de-diego_crisci_2022, title={Use of Crystal Violet to Improve Visual Cytopathic Effect- based Reading for Viral Titration using TCID50 Assays}, volume={2}, ISSN={["1940-087X"]}, DOI={10.3791/63063}, abstractNote={Viral titration is a key assay for virology research. The detection of cytopathic effect (CPE) via TCID50 assays and plaque-forming units (PFU) assays are the two main methods to calculate the titer of a virus stock and are often based on microscopy detection or cell staining for visualization. In the case of TCID50 assay, objective visualization is commonly based on immunocytochemical (ICC) staining of intracellular virus to calculate titers combined with visual CPE detection via microscopy. However, ICC staining is costly and time consuming. In this study, we compared visual CPE observation via microscopy, ICC staining and crystal violet staining to determine the titers of two CPE-forming viruses, Influenza A virus (IAV) of swine origin and Porcine Reproductive and Respiratory Syndrome virus (PRRSV). We show that both crystal violet and ICC staining are more accurate than visual CPE detection, presenting nearly identical levels of precision on both IAV and PRRSV. For this reason, here we present crystal violet staining as a faster and more affordable way to determine viral titrations on a TCID50 assay for CPE-forming viruses titrated in cell lines.}, number={180}, journal={JOVE-JOURNAL OF VISUALIZED EXPERIMENTS}, author={Frias-De-Diego, Alba and Crisci, Elisa}, year={2022}, month={Feb} }
 @article{kwon_cheeseman_frias-de-diego_hong_yang_jung_yin_murdoch_scholle_crook_et al._2021, title={A Liquid Metal Mediated Metallic Coating for Antimicrobial and Antiviral Fabrics}, volume={9}, ISSN={["1521-4095"]}, url={http://europepmc.org/abstract/med/34550628}, DOI={10.1002/adma.202104298}, abstractNote={Fabrics are widely used in hospitals and many other settings for bedding, clothing, and face masks; however, microbial pathogens can survive on surfaces for a long time, leading to microbial transmission. Coatings of metallic particles on fabrics have been widely used to eradicate pathogens. However, current metal particle coating technologies encounter numerous issues such as nonuniformity, processing complexity, and poor adhesion. To overcome these issues, an easy-to-control and straightforward method is reported to coat a wide range of fabrics by using gallium liquid metal (LM) particles to facilitate the deposition of liquid metal copper alloy (LMCu) particles. Gallium particles coated on the fabric provide nucleation sites for forming LMCu particles at room temperature via galvanic replacement of Cu2+ ions. The LM helps promote strong adhesion of the particles to the fabric. The presence of the LMCu particles can eradicate over 99% of pathogens (including bacteria, fungi, and viruses) within 5 min, which is significantly more effective than control samples coated with only Cu. The coating remains effective over multiple usages and against contaminated droplets and aerosols, such as those encountered in facemasks. This facile coating method is promising for generating robust antibacterial, antifungal, and antiviral fabrics and surfaces.}, journal={ADVANCED MATERIALS}, author={Kwon, Ki Yoon and Cheeseman, Samuel and Frias-De-Diego, Alba and Hong, Haeleen and Yang, Jiayi and Jung, Woojin and Yin, Hong and Murdoch, Billy J. and Scholle, Frank and Crook, Nathan and et al.}, year={2021}, month={Sep} }
 @article{svanberg_ellegård_crisci_khalid_borendal_svenvik_nyström_birse_burgener_shankar_et al._2021, title={Complement-Opsonized HIV Modulates Pathways Involved in Infection of Cervical Mucosal Tissues: A Transcriptomic and Proteomic Study.}, url={http://europepmc.org/abstract/med/34093520}, DOI={10.3389/fimmu.2021.625649}, abstractNote={Genital mucosal transmission is the most common route of HIV spread. The initial responses triggered at the site of viral entry are reportedly affected by host factors, especially complement components present at the site, and this will have profound consequences on the outcome and pathogenesis of HIV infection. We studied the initial events associated with host-pathogen interactions by exposing cervical biopsies to free or complement-opsonized HIV. Opsonization resulted in higher rates of HIV acquisition/infection in mucosal tissues and emigrating dendritic cells. Transcriptomic and proteomic data showed a significantly more pathways and higher expression of genes and proteins associated with viral replication and pathways involved in different aspects of viral infection including interferon signaling, cytokine profile and dendritic cell maturation for the opsonized HIV. Moreover, the proteomics data indicate a general suppression by the HIV exposure. This clearly suggests that HIV opsonization alters the initial signaling pathways in the cervical mucosa in a manner that promotes viral establishment and infection. Our findings provide a foundation for further studies of the role these early HIV induced events play in HIV pathogenesis.}, journal={Frontiers in immunology}, author={Svanberg, C and Ellegård, R and Crisci, E and Khalid, M and Borendal, Wodlin N and Svenvik, M and Nyström, S and Birse, K and Burgener, A and Shankar, EM and et al.}, year={2021}, month={May} }
 @article{svanberg_ellegård_crisci_khalid_wodlin_svenvik_nyström_birse_burgener_shankar_et al._2021, title={Corrigendum: Complement-Opsonized HIV Modulates Pathways Involved in Infection of Cervical Mucosal Tissues: A Transcriptomic and Proteomic Study.}, url={http://europepmc.org/abstract/med/34305955}, DOI={10.3389/fimmu.2021.730130}, journal={Frontiers in immunology}, author={Svanberg, C and Ellegård, R and Crisci, E and Khalid, M and Wodlin, NB and Svenvik, M and Nyström, S and Birse, K and Burgener, A and Shankar, EM and et al.}, year={2021}, month={Jul} }
 @article{kick_wolfe_amaral_cortes_almond_crisci_gauger_pittman_kaeser_2021, title={Maternal Autogenous Inactivated Virus Vaccination Boosts Immunity to PRRSV in Piglets}, volume={9}, ISSN={["2076-393X"]}, url={https://doi.org/10.3390/vaccines9020106}, DOI={10.3390/vaccines9020106}, abstractNote={Maternal-derived immunity is a critical component for the survival and success of offspring in pigs to protect from circulating pathogens such as Type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV-2). The purpose of this study is to investigate the transfer of anti-PRRSV immunity to piglets from gilts that received modified-live virus (MLV) alone (treatment (TRT) 0), or in combination with one of two autogenous inactivated vaccines (AIVs, TRT 1+2). Piglets from these gilts were challenged with the autogenous PRRSV-2 strain at two weeks of age and their adaptive immune response (IR) was evaluated until 4 weeks post inoculation (wpi). The systemic humoral and cellular IR was analyzed in the pre-farrow gilts, and in piglets, pre-inoculation, and at 2 and 4 wpi. Both AIVs partially protected the piglets with reduced lung pathology and increased weight gain; TRT 1 also lowered piglet viremia, best explained by the AIV-induced production of neutralizing antibodies in gilts and their transfer to the piglets. In piglets, pre-inoculation, the main systemic IFN-γ producers were CD21α+ B cells. From 0 to 4 wpi, the role of these B cells declined and CD4 T cells became the primary systemic IFN-γ producers. In the lungs, CD8 T cells were the primary and CD4 T cells were the secondary IFN-γ producers, including a novel subset of porcine CD8α−CCR7− CD4 T cells, potentially terminally differentiated CD4 TEMRA cells. In summary, this study demonstrates that maternal AIV vaccination can improve protection of pre-weaning piglets against PRRSV-2; it shows the importance of transferring neutralizing antibodies to piglets, and it introduces two novel immune cell subsets in pigs—IFN-γ producing CD21α+ B cells and CD8α−CCR7− CD4 T cells.}, number={2}, journal={VACCINES}, publisher={MDPI AG}, author={Kick, Andrew R. and Wolfe, Zoe C. and Amaral, Amanda E. and Cortes, Lizette M. and Almond, Glen W. and Crisci, Elisa and Gauger, Phillip C. and Pittman, Jeremy and Kaeser, Tobias}, year={2021}, month={Feb} }
 @article{kick_amaral_frias-de-diego_cortes_fogle_crisci_almond_käser_2021, title={The Local and Systemic Humoral Immune Response Against Homologous and Heterologous Strains of the Type 2 Porcine Reproductive and Respiratory Syndrome Virus}, volume={1}, url={http://europepmc.org/abstract/PMC/PMC7985350}, journal={Frontiers in immunology}, author={Kick, A and Amaral, A and Frias-De-Diego, A and Cortes, L and Fogle, J and Crisci, E and Almond, G and Käser, T}, year={2021}, month={Jan} }
 @article{kick_amaral_frias-de-diego_cortes_fogle_crisci_almond_kaser_2021, title={The Local and Systemic Humoral Immune Response Against Homologous and Heterologous Strains of the Type 2 Porcine Reproductive and Respiratory Syndrome Virus}, volume={12}, ISSN={["1664-3224"]}, DOI={10.3389/fimmu.2021.637613}, abstractNote={The humoral immune response plays a crucial role in the combat and protection against many pathogens including the economically most important, highly prevalent, and diverse pig pathogen PRRSV – the Porcine Reproductive and Respiratory Syndrome Virus. In addition to viremia and viral shedding analyses, this study followed the local and systemic humoral immune response of pigs for 63 days upon inoculation with one of three types of Type-2 PRRSV (PRRSV-2) strains – one modified live virus (MLV) vaccine strain, and two lineage 1 PRRSV-2 strains, NC134 and NC174. The local response was analyzed by quantifying immunoglobulin (Ig)A in nasal swabs. The systemic response was studied by the quantification of IgG with ELISA and homo- and heterologous neutralizing antibodies (NAs) utilizing a novel method of flow cytometry. In all PRRSV-2 inoculated groups, viral nasal shedding started at 3 dpi, peaked between 3 and 7 days post inoculation, and was cleared at 28–35 dpi with sporadic rebounds thereafter. The local IgA response started 4–7 days after viral shedding occurred and showed a bi-phasic course with peaks at 14 dpi and at 28–35 dpi. Of note, the NC134 and NC174 strains induced a much stronger local IgA response. As reported earlier, main viremia lasted from 7 dpi to 28 dpi (NC174), 42 dpi (NC134) or until the end of the study (MLV). Similar to the local IgA response, the systemic IgG response started 4–7 days after viremia; but in contrast to viremia, serum IgG levels stayed high for all PRRSV-2 inoculated groups until the end of the study. A significant finding was that while the serum NA response in the MLV group was delayed by 28 days, serum NAs in pigs infected with our two NC134 and NC174 strains could be detected as early as 7 dpi (NC134) and 14 dpi (NC174). Compared to homologous NA responses, the NA responses against heterologous strains was strong but slightly delayed between our lineage 1 one strains or non-existent between the MLV and lineage 1 strains. This study improves our understanding of the relationship between local and systemic infections and the humoral immune response induced by PRRSV-2 infection or MLV vaccination. Our data also provide novel insights into the timeline of the development of homologous and heterologous NA levels – by both MLV vaccination or infection with two strains from the currently prevalent PRRSV-2 lineage 1.}, journal={FRONTIERS IN IMMUNOLOGY}, author={Kick, Andrew R. and Amaral, Amanda F. and Frias-De-Diego, Alba and Cortes, Lizette M. and Fogle, Jonathan E. and Crisci, Elisa and Almond, Glen W. and Kaser, Tobias}, year={2021}, month={Mar} }
 @article{frias-de-diego_jara_pecoraro_crisci_2021, title={Whole Genome or Single Genes? A Phylodynamic and Bibliometric Analysis of PRRSV}, volume={8}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2021.658512}, abstractNote={Diversity, ecology, and evolution of viruses are commonly determined through phylogenetics, an accurate tool for the identification and study of lineages with different pathological characteristics within the same species. In the case of PRRSV, evolutionary research has divided into two main branches based on the use of a specific gene (i.e., ORF5) or whole genome sequences as the input used to produce the phylogeny. In this study, we performed a review on PRRSV phylogenetic literature and characterized the spatiotemporal trends in research of single gene vs. whole genome evolutionary approaches. Finally, using publicly available data, we produced a Bayesian phylodynamic analysis following each research branch and compared the results to determine the pros and cons of each particular approach. This study provides an exploration of the two main phylogenetic research lines applied for PRRSV evolution, as well as an example of the differences found when both methods are applied to the same database. We expect that our results will serve as a guidance for future PRRSV phylogenetic research.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Frias-De-Diego, Alba and Jara, Manuel and Pecoraro, Brittany M. and Crisci, Elisa}, year={2021}, month={Jun} }
 @article{frias-de-diego_posey_pecoraro_carnevale_beaty_crisci_2020, title={A Century of Swine Influenza: Is It Really Just about the Pigs?}, volume={7}, url={https://doi.org/10.3390/vetsci7040189}, DOI={10.3390/vetsci7040189}, abstractNote={Influenza viruses (IV) are one of the major threats to human and animal health worldwide due to the variety of species they affect. Pigs play an important role in IV ecology as the “mixing vessel,” since they can be infected by swine, avian and human IV, allowing the appearance of new subtypes. Human viruses originated in swine are known as IV of swine origin or swine influenza virus (SwIV) variants. In this study, we identified knowledge tendencies of SwIV and assessed potential bias in the literature caused by these variants. We identified the most mentioned SwIV variants and manually reviewed the literature to determine the number of publications applying the whole influenza nomenclature, a partial nomenclature, only the subtype or mixed terminology, along with the proportion of articles in which the GenBank ID number was available. We observed that the 2009 H1N1 human pandemic created an important bias in SwIV research driven by an increase in human publications on the IV of swine origin. H1N1 is the most studied subtype for swine and humans, followed by H3N2. We found differences between the nomenclatures applied, where partial classifications were slightly more common. Finally, from all the publications, only 25% stated the GenBank ID of the sequence studied. This review represents the most complete exploration of trends in SwIV knowledge to date and will serve as a guidance for future search strategies in SwIV research.}, number={4}, journal={Veterinary Sciences}, publisher={MDPI AG}, author={Frias-De-Diego, Alba and Posey, Rachael and Pecoraro, Brittany M. and Carnevale, Rafaella Fernandes and Beaty, Alayna and Crisci, Elisa}, year={2020}, month={Nov}, pages={189} }
 @article{distinctive cellular and metabolic reprogramming in porcine lung mononuclear phagocytes infected with type 1 prrsv strains._2020, url={https://europepmc.org/articles/PMC7750501}, DOI={10.3389/fimmu.2020.588411}, abstractNote={Porcine reproductive and respiratory syndrome (PRRS) has an extensive impact on pig production. The causative virus (PRRSV) is divided into two species, PRRSV-1 (European origin) and PRRSV-2 (North American origin). Within PRRSV-1, PRRSV-1.3 strains, such as Lena, are more pathogenic than PRRSV-1.1 strains, such as Flanders 13 (FL13). To date, the molecular interactions of PRRSV with primary lung mononuclear phagocyte (MNP) subtypes, including conventional dendritic cells types 1 (cDC1) and 2 (cDC2), monocyte-derived DCs (moDC), and pulmonary intravascular macrophages (PIM), have not been thoroughly investigated. Here, we analyze the transcriptome profiles of in vivo FL13-infected parenchymal MNP subpopulations and of in vitro FL13- and Lena-infected parenchymal MNP. The cell-specific expression profiles of in vivo sorted cells correlated with their murine counterparts (AM, cDC1, cDC2, moDC) with the exception of PIM. Both in vivo and in vitro , FL13 infection altered the expression of a low number of host genes, and in vitro infection with Lena confirmed the higher ability of this strain to modulate host response. Machine learning (ML) and gene set enrichment analysis (GSEA) unraveled additional relevant genes and pathways modulated by FL13 infection that were not identified by conventional analyses. GSEA increased the cellular pathways enriched in the FL13 data set, but ML allowed a more complete comprehension of functional profiles during FL13 in vitro infection. Data indicates that cellular reprogramming differs upon Lena and FL13 infection and that the latter might keep antiviral and inflammatory macrophage/DC functions silent. Although the slow replication kinetics of FL13 likely contribute to differences in cellular gene expression, the data suggest distinct mechanisms of interaction of the two viruses with the innate immune system during early infection.}, journal={Frontiers in immunology}, year={2020}, month={Dec} }
 @article{kick_wolfe_amaral_cortes_almond_crisci_gauger_pittman_käser_2020, title={Maternal Autogenous Inactivated Virus Vaccination Boosts the Piglet Humoral and Cell-Mediated Immunity to PRRSV via Transfer of Neutralizing Antibodies and Interferon-Gamma Producing B Cells}, volume={12}, url={https://doi.org/10.20944/preprints202012.0074.v1}, DOI={10.20944/preprints202012.0074.v1}, abstractNote={Maternal-derived immunity is a critical component for survival and success of offspring in pigs to protect from circulating pathogens like Type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV-2). The purpose of this study was to investigate the transfer of anti-PRRSV immunity to piglets from gilts that received modified-live virus (MLV) alone (TRT 0), or in combination with one of two autogenous inactivated vaccines (AIVs, TRT 1+2). Piglets from these gilts were challenged with the autogenous PRRSV-2 strain at two weeks of age and their adaptive immune response (IR) was evaluated until 4 weeks post inoculation (wpi). The systemic humoral and cellular IR was analyzed in the pre-farrow gilts, and in piglets, pre-inoculation, and at 2- and 4-wpi. Both AIVs partially protected the piglets with reduced lung pathology and increased weight gain; TRT 1 also lowered piglet viremia best explained by the AIV-induced production of neutralizing antibodies in gilts and their transfer to the piglets. In piglets, pre-inoculation, the main systemic IFN-γ producers were CD21α+ B cells. From 0 to 4 wpi, the role of these B cells declined and CD4 T cells became the primary systemic IFN-γ producers. In lungs, CD8 T cells were the primary and CD4 T cells the secondary IFN-γ producers including a novel subset of porcine CD8α-CCR7- CD4 T cells, potentially terminally differentiated CD4 TEMRA cells. In summary, this study demonstrates that maternal AIV vaccination can improve protection of pre-weaning piglets against PRRSV-2; it shows the importance of transferring neutralizing antibodies to piglets; and it introduces two novel immune cell subsets in pigs – IFN-γ producing CD21α+ B cells and CD8α-CCR7- CD4 T cells.}, publisher={MDPI AG}, author={Kick, Andrew R. and Wolfe, Zoe C. and Amaral, Amanda F. and Cortes, Lizette M. and Almond, Glen W. and Crisci, Elisa and Gauger, Phillip C. and Pittman, Jeremy and Käser, Tobias}, year={2020}, month={Dec} }
 @article{mach_ruet_clark_bars-cortina_ramayo-caldas_crisci_pennarun_dhorne-pollet_foury_moisan_et al._2020, title={Priming for welfare: gut microbiota is associated with equitation conditions and behavior in horse athletes}, volume={10}, ISSN={["2045-2322"]}, url={http://europepmc.org/abstract/med/32433513}, DOI={10.1038/s41598-020-65444-9}, abstractNote={Abstract We simultaneously measured the fecal microbiota and multiple environmental and host-related variables in a cohort of 185 healthy horses reared in similar conditions during a period of eight months. The pattern of rare bacteria varied from host to host and was largely different between two time points. Among a suite of variables examined, equitation factors were highly associated with the gut microbiota variability, evoking a relationship between gut microbiota and high levels of physical and mental stressors. Behavioral indicators that pointed toward a compromised welfare state ( e.g . stereotypies, hypervigilance and aggressiveness) were also associated with the gut microbiota, reinforcing the notion for the existence of the microbiota-gut-brain axis. These observations were consistent with the microbiability of behaviour traits (> 15%), illustrating the importance of gut microbial composition to animal behaviour. As more elite athletes suffer from stress, targeting the microbiota offers a new opportunity to investigate the bidirectional interactions within the brain gut microbiota axis.}, number={1}, journal={SCIENTIFIC REPORTS}, author={Mach, Nuria and Ruet, Alice and Clark, Allison and Bars-Cortina, David and Ramayo-Caldas, Yuliaxis and Crisci, Elisa and Pennarun, Samuel and Dhorne-Pollet, Sophie and Foury, Aline and Moisan, Marie-Pierre and et al.}, year={2020}, month={May} }
 @article{crisci_fraile_montoya_2019, title={Cellular Innate Immunity against PRRSV and Swine Influenza Viruses}, url={https://www.mdpi.com/2306-7381/6/1/26}, DOI={10.3390/vetsci6010026}, abstractNote={Porcine respiratory disease complex (PRDC) is a polymicrobial syndrome that results from a combination of infectious agents, such as environmental stressors, population size, management strategies, age, and genetics. PRDC results in reduced performance as well as increased mortality rates and production costs in the pig industry worldwide. This review focuses on the interactions of two enveloped RNA viruses—porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza virus (SwIV)—as major etiological agents that contribute to PRDC within the porcine cellular innate immunity during infection. The innate immune system of the porcine lung includes alveolar and parenchymal/interstitial macrophages, neutrophils (PMN), conventional dendritic cells (DC) and plasmacytoid DC, natural killer cells, and γδ T cells, thus the in vitro and in vivo interactions between those cells and PRRSV and SwIV are reviewed. Likewise, the few studies regarding PRRSV-SwIV co-infection are illustrated together with the different modulation mechanisms that are induced by the two viruses. Alterations in responses by natural killer (NK), PMN, or γδ T cells have not received much attention within the scientific community as their counterpart antigen-presenting cells and there are numerous gaps in the knowledge regarding the role of those cells in both infections. This review will help in paving the way for future directions in PRRSV and SwIV research and enhancing the understanding of the innate mechanisms that are involved during infection with these viruses.}, journal={Veterinary Sciences}, author={Crisci, Elisa and Fraile, Lorenzo and Montoya, Maria}, year={2019}, month={Mar} }
 @article{hsv-2 cellular programming enables productive hiv infection in dendritic cells_2019, url={http://dx.doi.org/10.3389/fimmu.2019.02889}, DOI={10.3389/fimmu.2019.02889}, abstractNote={Genital herpes is a common sexually transmitted infection caused by herpes simplex virus type 2 (HSV-2). Genital herpes significantly enhances the acquisition and transmission of HIV-1 by creating a microenvironment that supports HIV infection in the host. Dendritic cells (DCs) represent one of the first innate cell types that encounter HIV-1 and HSV-2 in the genital mucosa. HSV-2 infection has been shown to modulate DCs, rendering them more receptive to HIV infection. Here, we investigated the potential mechanisms underlying HSV-2-mediated augmentation of HIV-1 infection. We demonstrated that the presence of HSV-2 enhanced productive HIV-1 infection of DCs and boosted inflammatory and antiviral responses. The HSV-2 augmented HIV-1 infection required intact HSV-2 DNA, but not active HSV-2 DNA replication. Furthermore, the augmented HIV infection of DCs involved the cGAS-STING pathway. Interestingly, we could not see any involvement of TLR2 or TLR3 nor suppression of infection by IFN-β production. The conditioning by HSV-2 in dual exposed DCs decreased protein expression of IFI16, cGAS, STING, and TBK1, which is associated with signaling through the STING pathway. Dual exposure to HSV-2 and HIV-1 gave decreased levels of several HIV-1 restriction factors, especially SAMHD1, TREX1, and APOBEC3G. Activation of the STING pathway in DCs by exposure to both HSV-2 and HIV-1 most likely led to the proteolytic degradation of the HIV-1 restriction factors SAMHD1, TREX1, and APOBEC3G, which should release their normal restriction of HIV infection in DCs. This released their normal restriction of HIV infection in DCs. We showed that HSV-2 reprogramming of cellular signaling pathways and protein expression levels in the DCs provided a setting where HIV-1 can establish a higher productive infection in the DCs. In conclusion, HSV-2 reprogramming opens up DCs for HIV-1 infection and creates a microenvironment favoring HIV-1 transmission.}, journal={Frontiers in Immunology}, year={2019}, month={Dec} }
 @article{bordet_fretaud_crisci_bouguyon_rault_pezant_pleau_renson_giuffra_larcher_et al._2019, title={Macrophage-B Cell Interactions in the Inverted Porcine Lymph Node and Their Response to Porcine Reproductive and Respiratory Syndrome Virus}, volume={10}, ISSN={["1664-3224"]}, DOI={10.3389/fimmu.2019.00953}, abstractNote={Swine lymph nodes (LN) present an inverted structure compared to mouse and human, with the afferent lymph diffusing from the center to the periphery. This structure, also observed in close and distant species such as dolphins, hippopotamus, rhinoceros, and elephants, is poorly described, nor are the LN macrophage populations and their relationship with B cell follicles. B cell maturation occurs mainly in LN B cell follicles with the help of LN macrophage populations endowed with different antigen delivery capacities. We identified three macrophage populations that we localized in the inverted LN spatial organization. This allowed us to ascribe porcine LN MΦ to their murine counterparts: subcapsular sinus MΦ, medullary cord MΦ and medullary sinus MΦ. We identified the different intra and extrafollicular stages of LN B cells maturation and explored the interaction of MΦ, drained antigen and follicular B cells. The porcine reproductive and respiratory syndrome virus (PRRSV) is a major porcine pathogen that infects tissue macrophages (MΦ). PRRSV is persistent in the secondary lymphoid tissues and induces a delay in neutralizing antibodies appearance. We observed PRRSV interaction with two LN MΦ populations, of which one interacts closely with centroblasts. We observed BCL6 up-regulation in centroblast upon PRRSV infection, leading to new hypothesis on PRRSV inhibition of B cell maturation. This seminal study of porcine LN will permit fruitful comparison with murine and human LN for a better understanding of normal and inverted LN development and functioning.}, journal={FRONTIERS IN IMMUNOLOGY}, author={Bordet, Elise and Fretaud, Maxence and Crisci, Elisa and Bouguyon, Edwige and Rault, Stephane and Pezant, Jeremy and Pleau, Alexis and Renson, Patricia and Giuffra, Elisabetta and Larcher, Thibaut and et al.}, year={2019}, month={May} }
 @article{foissac_djebali_munyard_vialaneix_rau_muret_esquerré_zytnicki_derrien_bardou_et al._2019, title={Multi-species annotation of transcriptome and chromatin structure in domesticated animals.}, volume={12}, url={http://europepmc.org/abstract/med/31884969}, DOI={10.1186/s12915-019-0726-5}, abstractNote={Abstract Background Comparative genomics studies are central in identifying the coding and non-coding elements associated with complex traits, and the functional annotation of genomes is a critical step to decipher the genotype-to-phenotype relationships in livestock animals. As part of the Functional Annotation of Animal Genomes (FAANG) action, the FR-AgENCODE project aimed to create reference functional maps of domesticated animals by profiling the landscape of transcription (RNA-seq), chromatin accessibility (ATAC-seq) and conformation (Hi-C) in species representing ruminants (cattle, goat), monogastrics (pig) and birds (chicken), using three target samples related to metabolism (liver) and immunity (CD4+ and CD8+ T cells). Results RNA-seq assays considerably extended the available catalog of annotated transcripts and identified differentially expressed genes with unknown function, including new syntenic lncRNAs. ATAC-seq highlighted an enrichment for transcription factor binding sites in differentially accessible regions of the chromatin. Comparative analyses revealed a core set of conserved regulatory regions across species. Topologically associating domains (TADs) and epigenetic A/B compartments annotated from Hi-C data were consistent with RNA-seq and ATAC-seq data. Multi-species comparisons showed that conserved TAD boundaries had stronger insulation properties than species-specific ones and that the genomic distribution of orthologous genes in A/B compartments was significantly conserved across species. Conclusions We report the first multi-species and multi-assay genome annotation results obtained by a FAANG project. Beyond the generation of reference annotations and the confirmation of previous findings on model animals, the integrative analysis of data from multiple assays and species sheds a new light on the multi-scale selective pressure shaping genome organization from birds to mammals. Overall, these results emphasize the value of FAANG for research on domesticated animals and reinforces the importance of future meta-analyses of the reference datasets being generated by this community on different species.}, journal={BMC biology}, author={Foissac, S and Djebali, S and Munyard, K and Vialaneix, N and Rau, A and Muret, K and Esquerré, D and Zytnicki, M and Derrien, T and Bardou, P and et al.}, year={2019}, month={Dec} }
 @article{kick_amaral_cortes_fogle_crisci_almond_käser_2019, title={The T-Cell Response to Type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV)}, volume={11}, url={https://doi.org/10.3390/v11090796}, DOI={10.3390/v11090796}, abstractNote={Porcine reproductive and respiratory syndrome virus (PRRSV) continues to cause severe reproductive and respiratory pathologies resulting in immense monetary and welfare costs for the swine industry. The vaccines against PRRSV are available; but they struggle with providing protection against the plethora of heterologous PRRSV strains. To improve PRRSV vaccine development, the aim of this study was to provide an in-depth analysis of the crucial heterologous T-cell response to type-2 PRRSV. Following PRRSV modified live virus (MLV) vaccination or infection using one high- or one low-pathogenic PRRSV-strain, this nine-week study evaluated the T-cell response to different PRRSV strains. Our results demonstrate an important role for T cells in this homo- and heterologous response. Specifically, the T-helper cells were the main responders during viremia. Their peak response at 28 dpi correlated with a reduction in viremia, and their homing receptor expression indicated the additional importance for the anti-PRRSV response in the lymphatic and lung tissue. The cytotoxic T lymphocyte (CTL) response was the strongest at the site of infection—the lung and bronchoalveolar lavage. The TCR-γδ T cells were the main responders post viremia and PRRSV induced their expression of the lymph node homing the chemokine receptor, CCR7: This indicates a crucial role for TCR-γδ T cells in the anti-PRRSV response in the lymphatic system.}, number={9}, journal={Viruses}, publisher={MDPI AG}, author={Kick, Andrew and Amaral, Amanda and Cortes, Lizette and Fogle, Jonathan and Crisci, Elisa and Almond, Glen and Käser, Tobias}, year={2019}, month={Aug}, pages={796} }
 @article{dhorne-pollet_crisci_mach_renson_jaffrezic_marot_maroilley_moroldo_lecardonnel_blanc_et al._2019, title={The miRNA-targeted transcriptome of porcine alveolar macrophages upon infection with Porcine Reproductive and Respiratory Syndrome Virus}, volume={9}, ISSN={["2045-2322"]}, url={http://europepmc.org/abstract/med/30816147}, DOI={10.1038/s41598-019-39220-3}, abstractNote={Abstract Host miRNAs are known to modulate the cell response to virus infections. We characterized the miRNA-targeted transcriptome of porcine alveolar macrophages (PAMs) at early times after infection with a subtype 1.1 strain of PRRSV (Porcine Reproductive and Respiratory Syndrome Virus). We performed the immunoprecipitation of RISC (RNA-induced Silencing Complex) followed by microarray analysis of the RISC-bound miRNA targets (RIP-Chip) to evaluate the relative enrichment or depletion of expressed genes in RISC. The miRNA-mediated regulation occurred early after PRRSV infection and decreased fast (1,241 and 141 RISC-bound genes at 7 h and 10 h post-infection, respectively); it affected several cell functions with evidence of miRNA buffering of upregulated interferon-related genes. Eight miRNAs were highly enriched in RISC of both control and infected cells with no evidence of differential expression. Although miR-335-5p was the miRNA with most predicted targets among enriched RISC-bound genes, no effects on surface markers, cytokine expression and PRRSV replication were detected upon miR-335-5p mimics of primary PAMs. Our results do not point to specific miRNA-driven mechanisms regulating the early response to infection with this PRRSV 1.1 strain and indicate that the miRNome expressed by steady-state PAMs reacts promptly to counterbalance PRRSV infection by a pervasive modulation of host functions.}, journal={SCIENTIFIC REPORTS}, author={Dhorne-Pollet, Sophie and Crisci, Elisa and Mach, Nuria and Renson, Patricia and JaffreziC, Florence and Marot, Guillemette and Maroilley, Tatiana and Moroldo, Marco and Lecardonnel, Jerome and Blanc, Fany and et al.}, year={2019}, month={Feb} }
 @article{foissac_djebali_munyard_villa-vialaneix_rau_muret_esquerre_zytnicki_derrien_bardou_et al._2018, title={Livestock genome annotation: transcriptome and chromatin structure profiling in cattle, goat, chicken and pig.}, url={http://europepmc.org/abstract/PPR/PPR12967}, DOI={10.1101/316091}, abstractNote={Abstract Background Functional annotation of livestock genomes is a critical step to decipher the genotype-to-phenotype relationship underlying complex traits. As part of the Functional Annotation of Animal Genomes (FAANG) action, the FR-AgENCODE project ( http://www.fragencode.org ) aimed to profile the landscape of transcription (RNA-seq), chromatin accessibility (ATAC-seq) and conformation (Hi-C) in four livestock species representing ruminants (cattle, goat), monogastrics (pig) and birds (chicken), using three target samples related to metabolism (liver) and immunity (CD4+ and CD8+ T cells). Results RNA-seq assays considerably extended the available catalog of annotated transcripts and identified differentially expressed genes with unknown function, including new syntenic lncRNAs. ATAC-seq highlighted an enrichment for transcription factor binding sites in differentially accessible regions of the chromatin. Comparative analyses revealed a core set of conserved regulatory regions across species. Topologically Associating Domains (TADs) and epigenetic A/B compartments annotated from Hi-C data were consistent with RNA-seq and ATAC-seq data. Multi-species comparisons showed that conserved TAD boundaries had stronger insulation properties than species-specific ones and that the genomic distribution of orthologous genes in A/B compartments was significantly conserved across species. Conclusions We report the first multi-species and multi-assay genome annotation results obtained by a FAANG project. Beyond the generation of reference annotations and the confirmation of previous findings on model animals, the integrative analysis of data from multiple assays and species sheds a new light on the multi-scale selective pressure shaping genome organization from birds to mammals. Overall, these results emphasize the value of FAANG for research on domesticated animals and reinforces the importance of future meta-analyses of the reference datasets being generated by this community on different species.}, author={Foissac, S and Djebali, S and Munyard, K and Villa-Vialaneix, N and Rau, A and Muret, K and Esquerre, D and Zytnicki, M and Derrien, T and Bardou, P and et al.}, year={2018}, month={May} }
 @article{bordet_maisonnasse_renson_bouguyon_crisci_tiret_descamps_bernelin-cottet_urien_lefèvre_et al._2018, title={Porcine Alveolar Macrophage-like cells are pro-inflammatory Pulmonary Intravascular Macrophages that produce large titers of Porcine Reproductive and Respiratory Syndrome Virus.}, volume={7}, url={http://europepmc.org/abstract/med/29977043}, DOI={10.1038/s41598-018-28234-y}, abstractNote={Abstract Lung inflammation is frequently involved in respiratory conditions and it is strongly controlled by mononuclear phagocytes (MNP). We previously studied porcine lung MNP and described a new population of cells presenting all the features of alveolar macrophages (AM) except for their parenchymal location, that we named AM-like cells. Herein we showed that AM-like cells are macrophages phagocytosing blood-borne particles, in agreement with a pulmonary intravascular macrophages (PIM) identity. PIM have been described microscopically long time ago in species from the Laurasiatheria superorder such as bovine, swine, cats or cetaceans. We observed that PIM were more inflammatory than AM upon infection with the porcine reproductive and respiratory syndrome virus (PRRSV), a major swine pathogen. Moreover, whereas PRRSV was thought to mainly target AM, we observed that PIM were a major producer of virus. The PIM infection was more correlated with viremia in vivo than AM infection. Finally like AM, PIM-expressed genes were characteristic of an embryonic monocyte-derived macrophage population, whose turnover is independent of bone marrow-derived hematopoietic precursors. This last observation raised the interesting possibility that AM and PIM originate from the same lung precursor.}, journal={Scientific reports}, author={Bordet, E and Maisonnasse, P and Renson, P and Bouguyon, E and Crisci, E and Tiret, M and Descamps, D and Bernelin-Cottet, C and Urien, C and Lefèvre, F and et al.}, year={2018}, month={Jul} }
 @article{bordet_blanc_tiret_crisci_bouguyon_renson_maisonnasse_bourge_leplat_giuffra_et al._2018, title={Porcine Reproductive and Respiratory Syndrome Virus Type 1.3 Lena Triggers Conventional Dendritic Cells 1 Activation and T Helper 1 Immune Response Without Infecting Dendritic Cells}, volume={9}, ISSN={["1664-3224"]}, url={http://europepmc.org/abstract/med/30333837}, DOI={10.3389/fimmu.2018.02299}, abstractNote={Porcine Reproductive and Respiratory Syndrome virus (PRRSV) is an arterivirus responsible for highly contagious infection and huge economic losses in pig industry. Two PRRSV genotypes have been identified: the genotype 1 from European origin and the genotype 2 from North American origin. Genotypes 1 have been further divided into four subtypes. Genotype 1 subtype 3 (type 1.3) such as Lena are more pathogenic than type 1.1 such as Lelystad or Flanders13. One main feature of all PRRSV strains is their capacity to delay the appearance of neutralizing antibodies, leading to a viremia that can last several months. The role of the cellular immune response in PRRSV clearance remains ill defined, with type 1.3 viruses triggering a higher Th1 response than type 1.1 without striking differences in the viremia time course. It has been proposed that the inability of pigs to achieve rapid sterilizing immunity upon PRRSV infection might rely on the virus capacity to infect and inhibit dendritic cells (DCs) functions, as it has been observed for in vitro differentiated monocytes derived DCs (moDCs). The higher pathogeny of type 1.3 viruses compared with type 1.1 may also result from their differential ability to infect and/or activate DCs. However, the interactions of PRRSV with in vivo-differentiated-DC subtypes such as conventional DC1 (cDC1), cDC2 and moDCs have never been investigated. Here, the capacity of type 1 (Lelystad, Flanders13 and Lena) to infect DCs and to trigger differential T helper responses were compared. None of these 3 strains infected DCs neither in vivo nor in vitro. Moreover, Lena, but not LV and FL13, triggered cDC1 activation paralleled by a strong Th1 response. We thus propose that the ability of all PRRSV strains to alter the immune response is not due to the DCs infection or direct DCs inhibition.}, journal={FRONTIERS IN IMMUNOLOGY}, author={Bordet, Elise and Blanc, Fany and Tiret, Mathieu and Crisci, Elisa and Bouguyon, Edwige and Renson, Patricia and Maisonnasse, Pauline and Bourge, Mickael and Leplat, Jean-Jacques and Giuffra, Elisabetta and et al.}, year={2018}, month={Oct} }
 @article{hiv/human herpesvirus co-infections: impact on tryptophan-kynurenine pathway and immune reconstitution._2017, url={http://europepmc.org/abstract/med/29016635}, DOI={10.1371/journal.pone.0186000}, abstractNote={Background Co-infections with human herpesvirus (HHV) have been associated with residual chronic inflammation in antiretroviral (ART)-treated human immunodeficiency virus (HIV)-infected individuals. However, the role of HHV in modulating the tryptophan-kynurenine pathway and clinical outcomes in HIV-infected individuals is poorly understood. Thus, we investigated the seroprevalence of four common HHVs among treated HIV-infected participants and their impact on kynurenine/tryptophan (K/T) ratio and long-term CD4 T-cell recovery in HIV/HHV co-infected participants. Method In this cross-sectional study, HIV-infected participants receiving suppressive ART for a minimum of 12 months were recruited from the University Malaya Medical Centre (UMMC), Malaysia. Stored plasma was analyzed for CMV, VZV, HSV-1 and HSV-2 IgG antibody levels, immune activation markers (interleukin-6, interferon-γ, neopterin and sCD14), kynurenine and tryptophan concentrations. The influence of the number of HHV co-infection and K/T ratio on CD4 T-cell recovery was assessed using multivariate Poisson regression. Results A total of 232 HIV-infected participants were recruited and all participants were seropositive for at least one HHV; 96.1% with CMV, 86.6% with VZV, 70.7% with HSV-1 and 53.9% with HSV-2. K/T ratio had a significant positive correlation with CMV (rho = 0.205, p = 0.002), VZV (rho = 0.173, p = 0.009) and a tendency with HSV-2 (rho = 0.120, p = 0.070), with CMV antibody titer demonstrating the strongest modulating effect on K/T ratio among the four HHVs assessed in SOM analysis. In multivariate analysis, higher K/T ratio (p = 0.03) and increasing number of HHV co-infections (p<0.001) were independently associated with poorer CD4 T-cell recovery following 12 months of ART initiation. Conclusion Multiple HHV co-infections are common among ART-treated HIV-infected participants in the developing country setting and associated with persistent immune activation and poorer CD4 T-cell recovery.}, journal={PloS one}, year={2017} }
 @inproceedings{quelen_munyard_villa-vialaneix_cabau_rau_crisci_derrien_klopp_zytnicki_lagarrigue_et al._2017, title={Integrative and differential analysis of transcriptomes and chromatin accessibility regions reveals regulatory mechanisms involved in pig immune and metabolic functions}, booktitle={36th International Society for Animal Genetics Conference}, author={Quelen, Sarah Djebali and Munyard, Kylie and Villa-Vialaneix, Nathalie and Cabau, Cédric and Rau, Andrea and Crisci, Elisa and Derrien, Thomas and Klopp, Christophe and Zytnicki, Matthias and Lagarrigue, Sandrine and et al.}, year={2017}, pages={np} }
 @article{maisonnasse_bouguyon_bourge_piton_ezquerra_deloizy_urien_leplat_simon_chevalier_et al._2017, title={Pig as a biomedical model: Putting the porcine lung dendritic cells/macrophages network into light}, volume={34}, journal={Revue des Maladies Respiratoires}, publisher={Elsevier}, author={Maisonnasse, P and Bouguyon, E and Bourge, M and Piton, G and Ezquerra, A and Deloizy, C and Urien, C and Leplat, J-J and Simon, G and Chevalier, C and et al.}, year={2017}, pages={A328} }
 @article{crisci_ellegård_nyström_rondahl_serrander_bergström_sjöwall_eriksson_larsson_2016, title={Complement Opsonization Promotes Herpes Simplex Virus 2 Infection of Human Dendritic Cells}, volume={90}, url={https://doi.org/10.1128/JVI.00224-16}, DOI={10.1128/JVI.00224-16}, abstractNote={ABSTRACT Herpes simplex virus 2 (HSV-2) is one of the most common sexually transmitted infections globally, with a very high prevalence in many countries. During HSV-2 infection, viral particles become coated with complement proteins and antibodies, both present in genital fluids, which could influence the activation of immune responses. In genital mucosa, the primary target cells for HSV-2 infection are epithelial cells, but resident immune cells, such as dendritic cells (DCs), are also infected. DCs are the activators of the ensuing immune responses directed against HSV-2, and the aim of this study was to examine the effects opsonization of HSV-2, either with complement alone or with complement and antibodies, had on the infection of immature DCs and their ability to mount inflammatory and antiviral responses. Complement opsonization of HSV-2 enhanced both the direct infection of immature DCs and their production of new infectious viral particles. The enhanced infection required activation of the complement cascade and functional complement receptor 3. Furthermore, HSV-2 infection of DCs required endocytosis of viral particles and their delivery into an acid endosomal compartment. The presence of complement in combination with HSV-1- or HSV-2-specific antibodies more or less abolished HSV-2 infection of DCs. Our results clearly demonstrate the importance of studying HSV-2 infection under conditions that ensue in vivo , i.e., conditions under which the virions are covered in complement fragments and complement fragments and antibodies, as these shape the infection and the subsequent immune response and need to be further elucidated. IMPORTANCE During HSV-2 infection, viral particles should become coated with complement proteins and antibodies, both present in genital fluids, which could influence the activation of the immune responses. The dendritic cells are activators of the immune responses directed against HSV-2, and the aim of this study was to examine the effects of complement alone or complement and antibodies on HSV-2 infection of dendritic cells and their ability to mount inflammatory and antiviral responses. Our results demonstrate that the presence of antibodies and complement in the genital environment can influence HSV-2 infection under in vitro conditions that reflect the in vivo situation. We believe that our findings are highly relevant for the understanding of HSV-2 pathogenesis.}, number={10}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Crisci, Elisa and Ellegård, Rada and Nyström, Sofia and Rondahl, Elin and Serrander, Lena and Bergström, Tomas and Sjöwall, Christopher and Eriksson, Kristina and Larsson, Marie}, editor={Jung, J. U.Editor}, year={2016}, month={May}, pages={4939–4950} }
 @article{moreno_mena_angulo_gómez_crisci_montoya_blanco_bárcena_2016, title={Rabbit hemorrhagic disease virus capsid, a versatile platform for foreign B-cell epitope display inducing protective humoral immune responses.}, volume={6}, url={http://europepmc.org/abstract/med/27549017}, journal={Scientific reports}, author={Moreno, N and Mena, I and Angulo, I and Gómez, Y and Crisci, E and Montoya, M and Blanco, E and Bárcena, J}, year={2016}, pages={31844,} }
 @article{ellegård_crisci_andersson_shankar_nyström_hinkula_larsson_2015, title={Impaired NK Cell Activation and Chemotaxis toward Dendritic Cells Exposed to Complement-Opsonized HIV-1.}, url={http://europepmc.org/abstract/med/26157174}, DOI={10.4049/jimmunol.1500618}, abstractNote={Mucosa resident dendritic cells (DCs) may represent one of the first immune cells that HIV-1 encounters during sexual transmission. The virions in body fluids can be opsonized with complement factors because of HIV-mediated triggering of the complement cascade, and this appears to influence numerous aspects of the immune defense targeting the virus. One key attribute of host defense is the ability to attract immune cells to the site of infection. In this study, we investigated whether the opsonization of HIV with complement (C-HIV) or a mixture of complement and Abs (CI-HIV) affected the cytokine and chemokine responses generated by DCs, as well as their ability to attract other immune cells. We found that the expression levels of CXCL8, CXCL10, CCL3, and CCL17 were lowered after exposure to either C-HIV or CI-HIV relative to free HIV (F-HIV). DCs exposed to F-HIV induced higher cell migration, consisting mainly of NK cells, compared with opsonized virus, and the chemotaxis of NK cells was dependent on CCL3 and CXCL10. NK cell exposure to supernatants derived from HIV-exposed DCs showed that F-HIV induced phenotypic activation (e.g., increased levels of TIM3, CD69, and CD25) and effector function (e.g., production of IFNγ and killing of target cells) in NK cells, whereas C-HIV and CI-HIV did not. The impairment of NK cell recruitment by DCs exposed to complement-opsonized HIV and the lack of NK activation may contribute to the failure of innate immune responses to control HIV at the site of initial mucosa infection.}, note={: 1950), 2015}, journal={Journal of immunology (Baltimore}, author={Ellegård, R and Crisci, E and Andersson, J and Shankar, EM and Nyström, S and Hinkula, J and Larsson, M}, year={2015}, month={Jul} }
 @article{maisonnasse_bouguyon_piton_ezquerra_urien_deloizy_bourge_leplat_simon_chevalier_et al._2015, title={The respiratory DC/macrophage network at steady-state and upon influenza infection in the swine biomedical model.}, url={http://europepmc.org/abstract/med/26530136}, DOI={10.1038/mi.2015.105}, abstractNote={Human and mouse respiratory tracts show anatomical and physiological differences, which will benefit from alternative experimental models for studying many respiratory diseases. Pig has been recognized as a valuable biomedical model, in particular for lung transplantation or pathologies such as cystic fibrosis and influenza infection. However, there is a lack of knowledge about the porcine respiratory immune system. Here we segregated and studied six populations of pig lung dendritic cells (DCs)/macrophages (Mθs) as follows: conventional DCs (cDC) 1 and cDC2, inflammatory monocyte-derived DCs (moDCs), monocyte-derived Mθs, and interstitial and alveolar Mθs. The three DC subsets present migratory and naive T-cell stimulation capacities. As observed in human and mice, porcine cDC1 and cDC2 were able to induce T-helper (Th)1 and Th2 responses, respectively. Interestingly, porcine moDCs increased in the lung upon influenza infection, as observed in the mouse model. Pig cDC2 shared some characteristics observed in human but not in mice, such as the expression of FCɛRIα and Langerin, and an intra-epithelial localization. This work, by unraveling the extended similarities of the porcine and human lung DC/Mθ networks, highlights the relevance of pig, both as an exploratory model of DC/Mθ functions and as a model for human inflammatory lung pathologies.}, journal={Mucosal immunology}, author={Maisonnasse, P and Bouguyon, E and Piton, G and Ezquerra, A and Urien, C and Deloizy, C and Bourge, M and Leplat, JJ and Simon, G and Chevalier, C and et al.}, year={2015}, month={Nov} }
 @article{ellegård_crisci_burgener_sjöwall_birse_westmacott_hinkula_lifson_larsson_2014, title={Complement Opsonization of HIV-1 Results in Decreased Antiviral and Inflammatory Responses in Immature Dendritic Cells via CR3.}, volume={193}, url={http://europepmc.org/abstract/med/25252956}, DOI={10.4049/jimmunol.1401781}, abstractNote={Immature dendritic cells (iDCs) in genital and rectal mucosa may be one of the first cells to come into contact with HIV-1 during sexual transmission of virus. HIV-1 activates the host complement system, which results in opsonization of virus by inactivated complement fragments, for example, iC3b. We investigated antiviral and inflammatory responses induced in human iDCs after exposure to free HIV-1 (F-HIV), complement-opsonized HIV-1 (C-HIV), and complement and Ab-opsonized HIV-1 (CI-HIV). F-HIV gave rise to a significantly higher expression of antiviral factors such as IFN-β, myxovirus resistance protein A, and IFN-stimulated genes, compared with C-HIV and CI-HIV. Additionally, F-HIV induced inflammatory factors such as IL-1β, IL-6, and TNF-α, whereas these responses were weakened or absent after C-HIV or CI-HIV exposure. The responses induced by F-HIV were TLR8-dependent with subsequent activation of IFN regulatory factor 1, p38, ERK, PI3K, and NF-κB pathways, whereas these responses were not induced by C-HIV, which instead induced activation of IFN regulatory factor 3 and Lyn. This modulation of TLR8 signaling was mediated by complement receptor 3 and led to enhanced infection. The impact that viral hijacking of the complement system has on iDC function could be an important immune evasion mechanism used by HIV-1 to establish infection in the host.}, note={Baltimore, Md. : 1950),}, number={9}, journal={Journal of immunology}, author={Ellegård, R and Crisci, E and Burgener, A and Sjöwall, C and Birse, K and Westmacott, G and Hinkula, J and Lifson, JD and Larsson, M}, year={2014}, month={Nov}, pages={4590–4601} }
 @article{crisci_fraile_valentino_martínez-guinó_bottazzi_mantovani_montoya_2014, title={Immune characterization of long pentraxin 3 in pigs infected with influenza virus.}, volume={168}, url={http://europepmc.org/abstract/med/24238985}, DOI={10.1016/j.vetmic.2013.10.004}, abstractNote={Long pentraxin 3 (PTX3) is a conserved pattern-recognition secreted protein and a host-defence-related component of the humoral innate immune system. The aim of the present study was to characterize swine PTX3 (SwPTX3) protein expression in influenza virus infected pigs. First, we performed in silico studies to evaluate the cross-reactivity of PTX3 human antibodies against SwPTX3. Secondly, we used in vitro analysis to detect SwPTX3 presence in swine bone marrow dendritic cells (SwBMDC) upon stimulation with different agents by Western blot and immunofluorescence. Finally, the levels of SwPTX3 were assessed in experimental infection of pigs with different strains of influenza virus. This is a novel study where the expression of SwPTX3 was evaluated in the context of a pathogen infection. The initial characterization of SwPTX3 in influenza virus infected pigs contributes to understand the role of PTX proteins in the immune response.}, number={1}, journal={Veterinary microbiology}, author={Crisci, E and Fraile, L and Valentino, S and Martínez-Guinó, L and Bottazzi, B and Mantovani, A and Montoya, M}, year={2014}, month={Jan}, pages={185–192} }
 @article{crisci_fraile_novellas_espada_cabezón_martínez_cordoba_bárcena_benitez-ribas_montoya_2014, title={In vivo tracking and immunological properties of pulsed porcine monocyte-derived dendritic cells.}, url={http://europepmc.org/abstract/med/25282042}, DOI={10.1016/j.molimm.2014.08.006}, abstractNote={Cellular therapies using immune cells and in particular dendritic cells (DCs) are being increasingly applied in clinical trials and vaccines. Their success partially depends on accurate delivery of cells to target organs or migration to lymph nodes. Delivery and subsequent migration of cells to regional lymph nodes is essential for effective stimulation of the immune system. Thus, the design of an optimal DC therapy would be improved by optimizing technologies for monitoring DC trafficking. Magnetic resonance imaging (MRI) represents a powerful tool for non-invasive imaging of DC migration in vivo. Domestic pigs share similarities with humans and represent an excellent animal model for immunological studies. The aim of this study was to investigate the possibility using pigs as models for DC tracking in vivo. Porcine monocyte derived DC (MoDC) culture with superparamagnetic iron oxide (SPIO) particles was standardized on the basis of SPIO concentration and culture viability. Phenotype, cytokine production and mixed lymphocyte reaction assay confirmed that porcine SPIO-MoDC culture were similar to mock MoDCs and fully functional in vivo. Alike, similar patterns were obtained in human MoDCs. After subcutaneous inoculation in pigs, porcine SPIO-MoDC migration to regional lymph nodes was detected by MRI and confirmed by Perls staining of draining lymph nodes. Moreover, after one dose of virus-like particles-pulsed MoDCs specific local and systemic responses were confirmed using ELISPOT IFN-γ in pigs. In summary, the results in this work showed that after one single subcutaneous dose of pulsed MoDCs, pigs were able to elicit specific local and systemic immune responses. Additionally, the dynamic imaging of MRI-based DC tracking was shown using SPIO particles. This proof-of-principle study shows the potential of using pigs as a suitable animal model to test DC trafficking with the aim of improving cellular therapies.}, journal={Molecular immunology}, author={Crisci, E and Fraile, L and Novellas, R and Espada, Y and Cabezón, R and Martínez, J and Cordoba, L and Bárcena, J and Benitez-Ribas, D and Montoya, M}, year={2014}, month={Oct} }
 @article{crisci_mussá_fraile_montoya_2013, title={Review: influenza virus in pigs.}, volume={55}, url={http://europepmc.org/abstract/med/23523121}, DOI={10.1016/j.molimm.2013.02.008}, abstractNote={Influenza virus disease still remains one of the major threats to human health, involving a wide range of animal species and pigs play an important role in influenza ecology. Pigs were labeled as "mixing vessels" since they are susceptible to infection with avian, human and swine influenza viruses and genetic reassortment between these viruses can occur. After the H1N1 influenza pandemic of 2009 with a swine origin virus, the most recent research in "influenzology" is directed at improving knowledge of porcine influenza virus infection. This tendency is probably due to the fact that domestic pigs are closely related to humans and represent an excellent animal model to study various microbial infectious diseases. In spite of the role of the pig in influenza virus ecology, swine immune responses against influenza viruses are not fully understood. Considering these premises, the aim of this review is to focus on the in vitro studies performed with porcine cells and influenza virus and on the immune responses of pigs against human, avian and swine influenza viruses in vivo. The increased acceptance of pigs as suitable and valuable models in the scientific community may stimulate the development of new tools to assess porcine immune responses, paving the way for their consideration as the future "gold standard" large-animal model in immunology.}, number={3-4}, journal={Molecular immunology}, author={Crisci, E and Mussá, T and Fraile, L and Montoya, M}, year={2013}, month={Oct}, pages={200–211} }
 @article{seudopart́ıculas virales como vacunas v́ıricas en veterinaria_2013, journal={Inmunoloǵıa (1987)}, year={2013}, pages={102–106} }
 @article{crisci_bárcena_montoya_2013, title={Virus-like particle-based vaccines for animal viral infections}, volume={32}, DOI={10.1016/j.inmuno.2012.08.002}, abstractNote={Vaccination is considered one of the most effective ways to control pathogens and prevent diseases in humans as well as in the veterinary field. Traditional vaccines against animal viral diseases are based on inactivated or attenuated viruses, but new subunit vaccines are gaining attention from researchers in animal vaccinology. Among these, virus-like particles (VLPs) represent one of the most appealing approaches opening up interesting frontiers in animal vaccines. VLPs are robust protein scaffolds exhibiting well-defined geometry and uniformity that mimic the overall structure of the native virions but lack the viral genome. They are often antigenically indistinguishable from the virus from which they were derived and present important advantages in terms of safety. VLPs can stimulate strong humoral and cellular immune responses and have been shown to exhibit self-adjuvanting abilities. In addition to their suitability as a vaccine for the homologous virus from which they are derived, VLPs can also be used as vectors for the multimeric presentation of foreign antigens. VLPs have therefore shown dramatic effectiveness as candidate vaccines; nevertheless, only one veterinary VLP-base vaccine is licensed. Here, we review and examine in detail the current status of VLPs as a vaccine strategy in the veterinary field, and discuss the potential advantages and challenges of this technology. La vacunación constituye uno de los procedimientos más eficaces para controlar los patógenos y prevenir enfermedades tanto en seres humanos como en el campo veterinario. Las vacunas tradicionales frente a enfermedades animales se basan por lo general en la utilización de virus atenuados o inactivados. Sin embargo, las vacunas de subunidad están ganando terreno progresivamente en el campo de la sanidad animal. Entre ellas, las vacunas basadas en pseudopartículas virales o VLPs (por su nombre en inglés virus-like particles), representan una de las estrategias más atractivas actualmente en el campo de las vacunas para animales. Las VLPs son estructuras proteicas con una geometría y uniformidad muy definidas, que mimetizan la estructura de los virus nativos pero carecen de genoma viral. Por lo general son antigénicamente indistinguibles de los virus de los que proceden y su empleo como inmunógenos presenta importantes ventajas en términos de seguridad. Las VLPs pueden inducir una fuerte respuesta inmune, tanto humoral como celular, y se ha demostrado que poseen capacidad de actuar como adyuvantes (self-adjuvanting). Además de su idoneidad como vacunas frente al virus homólogo del cual proceden, las VLPs también se pueden utilizar como vectores para la presentación multimérica de antígenos heterólogos. Las VLPs han mostrado una elevada eficacia como candidatos vacunales, sin embargo, hasta el momento sólo una vacuna basada en VLPs ha sido autorizada y comercializada en el campo veterinario. En este trabajo se revisa el estado actual de las VLP empleadas como nuevas estrategias vacunales en el campo de la veterinaria, analizando las potenciales ventajas y desafíos que enfrenta esta tecnología.}, number={3}, journal={Inmunología}, publisher={Elsevier BV}, author={Crisci, Elisa and Bárcena, Juan and Montoya, María}, year={2013}, month={Jul}, pages={102–116} }
 @article{crisci_fraile_moreno_blanco_cabezón_costa_mussá_baratelli_martinez-orellana_ganges_et al._2012, title={Chimeric calicivirus-like particles elicit specific immune responses in pigs.}, volume={30}, url={http://europepmc.org/abstract/med/22306796}, DOI={10.1016/j.vaccine.2012.01.069}, abstractNote={Virus-like particles (VLPs) have received considerable attention due to their potential application in veterinary vaccines and, in particular, VLPs from rabbit haemorrhagic disease virus (RHDV) have successfully shown to be good platforms for inducing immune responses against an inserted foreign epitope in mice. The aim of this study was to assess the immunogenicity of chimeric RHDV-VLPs as vaccine vectors in pigs. For this purpose, we have generated chimeric VLPs containing a well-known T epitope of 3A protein of foot-and-mouth disease virus (FMDV). Firstly, RHDV-VLPs were able to activate immature porcine bone marrow-derived dendritic cells (poBMDCs) in vitro. Secondly, pigs were inoculated twice in a two-week interval with chimeric RHDV-VLPs at different doses intranasally or intramuscularly. One intramuscularly treated group was also inoculated with adjuvant Montanide™ ISA 206 at the same time. Specific IgG and IgA antibodies against RHDV-VLPs were induced and such levels were higher in the adjuvanted group compared with other groups. Interestingly, anti-RHDV-VLP IgA responses were higher in groups inoculated intramuscularly than those that received the VLPs intranasally. Two weeks after the last immunisation, specific IFN-γ-secreting cells against 3A epitope and against RHDV-VLPs were detected in PBMCs by ELISPOT. The adjuvanted group exhibited the highest IFN-γ-secreting cell numbers and lymphoproliferative specific T cell responses against 3A epitope and RHDV-VLP. This is the first immunological report on the potential use of chimeric RHDV-VLPs as antigen carriers in pigs.}, number={14}, author={Crisci, E. and Fraile, L. and Moreno, N. and Blanco, E. and Cabezón, R. and Costa, C. and Mussá, T. and Baratelli, M. and Martinez-Orellana, P. and Ganges, L. and et al.}, year={2012}, month={Mar}, pages={2427–2439} }
 @article{crisci_segalés coma_2012, title={Immunogenic properties of calicivirus-like particles as vaccine vectors}, publisher={Universitat Autònoma de Barcelona. Departament de Sanitat i d’Anatomia Animals,}, author={Crisci, Elisa and Segalés Coma, Joaquim}, year={2012} }
 @article{fraile_crisci_córdoba_navarro_osada_montoya_2012, title={Immunomodulatory properties of beta-sitosterol in pig immune responses.}, volume={13}, url={http://europepmc.org/abstract/med/22595193}, DOI={10.1016/j.intimp.2012.04.017}, abstractNote={The ability to control an immune response for the benefit and production efficiency of animals is the objective of immunomodulation in food-producing animals; substances that exert this control are called immunomodulators. A Spanish product (Inmunicín MAYMO®), based on food plant phytosterols, is being commercialized as complementary feed. The main component of this product is Beta-sitosterol (BSS). BSS and its glycoside (BSSG) have been shown to exhibit anti-inflammatory, anti-neoplasic, anti-pyretic and immune-modulating activity demonstrated by in vitro and in vivo experiments. The objective of the present study was to characterize the effect of BSS on the pig immune system using in vitro cell cultures first and to elucidate whether BSS possesses any in vivo activity in fattener pigs after vaccination with porcine reproductive and respiratory syndrome virus (PRRSV) modified life vaccine (MLV). Firstly, our in vitro results showed that BSS increased viable peripheral blood mononuclear cell (PBMC) numbers and it activated swine dendritic cells (DCs) in culture. Secondly, pigs treated with phytosterols prior to vaccination with PRRSV-MLV vaccine exhibited some changes in immunological parameters at different times post-vaccination, such as the proliferation ability of PBMC after phytohemaglutinin stimulation and increased apolipoprotein A1 plasma concentration which may contribute to enhance PRRSV vaccine response. In conclusion, the data in this report show that BSS can be considered an immunomodulator in pigs.}, number={3}, journal={International immunopharmacology}, author={Fraile, L and Crisci, E and Córdoba, L and Navarro, MA and Osada, J and Montoya, M}, year={2012}, month={Jul}, pages={316–321} }
 @article{crisci_bárcena_montoya_2012, title={Virus-like particles: the new frontier of vaccines for animal viral infections.}, volume={148}, url={http://europepmc.org/abstract/med/22705417}, DOI={10.1016/j.vetimm.2012.04.026}, abstractNote={Vaccination continues to be the main approach to protect animals from infectious diseases. Until recently, all licensed vaccines were developed using conventional technologies. Subunit vaccines are, however, gaining attention from researchers in the field of veterinary vaccinology, and among these, virus-like particles (VLPs) represent one of the most appealing approaches. VLPs are robust protein cages in the nanometer range that mimic the overall structure of the native virions but lack the viral genome. They are often antigenically indistinguishable from the virus from which they were derived and present important advantages in terms of safety. VLPs can stimulate strong humoral and cellular immune responses and have been shown to exhibit self-adjuvanting abilities. In addition to their suitability as a vaccine for the homologous virus from which they are derived, VLPs can also be used as vectors for the multimeric presentation of foreign antigens. VLPs have therefore shown dramatic effectiveness as candidate vaccines. Here, we review the current status of VLPs as a vaccine technology in the veterinary field, and discuss the potential advantages and challenges of this technology.}, number={3-4}, journal={Veterinary immunology and immunopathology}, author={Crisci, E and Bárcena, J and Montoya, M}, year={2012}, month={Aug}, pages={211–225} }
 @article{martinez-orellana_cortes_rodriguez-carino_córdoba_maeso_crisci_chamorro_martinez_dominguez_montoya_2012, title={phenoypical characterization and isolation of a subpopulation of myeloid cells from swine peripheral blood: new method to isolate plasmacytoid dendritic cells: p0920}, volume={137}, journal={Immunology}, publisher={Immunology}, author={Martinez-Orellana, P and Cortes, M and Rodriguez-Carino, C and Córdoba, L and Maeso, R and Crisci, E and Chamorro, S and Martinez, P and Dominguez, J and Montoya, M}, year={2012}, pages={482} }
 @article{bastos_benitez-ribas_crisci_naranjo_pérez-cabezas_montoya_2011, title={DC2010: Forum on Vaccine Science}, volume={30}, DOI={10.1016/j.inmuno.2011.05.002}, number={3}, journal={Inmunología}, publisher={Elsevier BV}, author={Bastos, Patricia and Benitez-Ribas, Daniel and Crisci, Elisa and Naranjo, Mar and Pérez-Cabezas, Begoña and Montoya, Maria}, year={2011}, month={Jul}, pages={100–104} }
 @article{mussá_rodriguez-cariño_pujol_córdoba_busquets_crisci_dominguez_fraile_montoya_2011, title={Interaction of porcine conventional dendritic cells with swine influenza virus.}, volume={420}, url={http://europepmc.org/abstract/med/21962444}, DOI={10.1016/j.virol.2011.09.001}, abstractNote={Swine influenza virus (SwIV) causes sub-acute or acute respiratory infections on swine farms and pigs can act as “mixing vessels” for new influenza strains. Knowledge of the immune response of SwIV in its natural host, pigs, is very limited. Dendritic cells (DCs) mediate the induction of immunity to pathogens, but their interaction with SwIV has not been fully characterized. Thus, porcine bone marrow derived DCs (poBMDCs) were exposed to a circulating strain of H3N2 SwIV in vitro . Infection of poBMDCs resulted in structures resembling influenza virus inside poBMDCs in vesicles and also free in cytoplasm. Viral progeny was undetectable in supernatant but limited replication was detected in the first 8 h after infection. However, viral particles from infected-poBMDCs were able to induce cytopathic effect in susceptible cells only when cell-to-cell interaction was favoured. The data generated in our studies reveal the particular interaction of H3N2 SwIV with conventional DCs.}, number={2}, author={Mussá, T and Rodriguez-Cariño, C and Pujol, M and Córdoba, L and Busquets, N and Crisci, E and Dominguez, J and Fraile, L and Montoya, M}, year={2011}, month={Nov}, pages={125–134} }
 @article{grau-roma_crisci_sibila_lopez-soria_nofrarı́as m_cortey_fraile_olvera_segales_2010, title={Corrigendum to “A proposal on porcine circovirus type 2 (PCV2) genotype definition and their relation with postweaning multisystemic wasting syndrome (PMWS) occurrence”[Vet. Microbiol. 128 (2008) 23--25]}, volume={141}, number={1}, journal={Veterinary Microbiology}, author={Grau-Roma, L and Crisci, E and Sibila, M and Lopez-Soria, S and Nofrarı́as M and Cortey, M and Fraile, L and Olvera, A and Segales, J}, year={2010}, pages={194} }
 @article{crisci_montoya gonzález_2010, title={Estudien el paper de la citoquina IL-10 en el desenvolupament de la circovirosi porcina}, journal={UAB divulga}, author={Crisci, Elisa and Montoya González, Maria}, year={2010}, pages={0001–2} }
 @article{busquets_segalés_córdoba_mussá_crisci_martín-valls_simon-grifé_pérez-simó_pérez-maíllo_núñez_et al._2010, title={Experimental infection with H1N1 European swine influenza virus protects pigs from an infection with the 2009 pandemic H1N1 human influenza virus.}, volume={41}, url={http://europepmc.org/abstract/med/20663475}, DOI={10.1051/vetres/2010046}, abstractNote={The recent pandemic caused by human influenza virus A(H1N1) 2009 contains ancestral gene segments from North American and Eurasian swine lineages as well as from avian and human influenza lineages. The emergence of this A(H1N1) 2009 poses a potential global threat for human health and the fact that it can infect other species, like pigs, favours a possible encounter with other influenza viruses circulating in swine herds. In Europe, H1N1, H1N2 and H3N2 subtypes of swine influenza virus currently have a high prevalence in commercial farms. To better assess the risk posed by the A(H1N1) 2009 in the actual situation of swine farms, we sought to analyze whether a previous infection with a circulating European avian-like swine A/Swine/Spain/53207/2004 (H1N1) influenza virus (hereafter referred to as SwH1N1) generated or not cross-protective immunity against a subsequent infection with the new human pandemic A/Catalonia/63/2009 (H1N1) influenza virus (hereafter referred to as pH1N1) 21 days apart. Pigs infected only with pH1N1 had mild to moderate pathological findings, consisting on broncho-interstitial pneumonia. However, pigs inoculated with SwH1N1 virus and subsequently infected with pH1N1 had very mild lung lesions, apparently attributed to the remaining lesions caused by SwH1N1 infection. These later pigs also exhibited boosted levels of specific antibodies. Finally, animals firstly infected with SwH1N1 virus and latter infected with pH1N1 exhibited undetectable viral RNA load in nasal swabs and lungs after challenge with pH1N1, indicating a cross-protective effect between both strains.}, number={5}, journal={Veterinary research}, author={Busquets, N and Segalés, J and Córdoba, L and Mussá, T and Crisci, E and Martín-Valls, GE and Simon-Grifé, M and Pérez-Simó, M and Pérez-Maíllo, M and Núñez, JI and et al.}, year={2010}, pages={74} }
 @article{increased numbers of myeloid and lymphoid il-10 producing cells in spleen of pigs with naturally occurring postweaning multisystemic wasting syndrome_2010, volume={136}, number={3-4}, journal={Veterinary immunology and immunopathology}, publisher={Elsevier}, year={2010}, pages={305–310} }
 @article{crisci_ballester_domínguez_segalés_montoya_2010, title={Increased numbers of myeloid and lymphoid IL-10 producing cells in spleen of pigs with naturally occurring postweaning multisystemic wasting syndrome.}, volume={136}, url={http://europepmc.org/abstract/med/20381172}, DOI={10.1016/j.vetimm.2010.03.008}, abstractNote={Porcine circovirus type 2 (PCV2) is the essential etiological agent of postweaning multisystemic wasting syndrome (PMWS), a worldwide distributed pig disease. The involvement of the immune system in the pathogenesis of PMWS is considered crucial. Previous studies have shown a cytokine profile suggesting T immunosuppression and indicating that interleukin 10 (IL-10) may play an important role during PCV2 infection. Nine 11- to 12-week-old conventional pigs were obtained from commercial farms located in North-Eastern Spain with historical records of PMWS. Spleen from four healthy and five PMWS-affected animals were collected at the necropsy. Viral load was determined in serum by means of standard PCR and real-time quantitative PCR. Phenotype and distribution of different immune cells involved in IL-10 secretion in the spleen of studied pigs were analysed using immunofluorescent assays. The CD163(+), CD4(+), and CD8(+) cell subpopulations produced IL-10 in the spleen and IL-10(+) cell numbers were higher in PMWS animals compared with their healthy counterparts. Furthermore, IL-10 producing cells were not infected by PCV2 and were mainly localized in the periarteriolar lymphoid sheaths. This is the first immunophenotyping study on IL-10 producing cells in cases of PMWS, further extending the studies on the role of IL-10 in disease pathogenesis.}, number={3-4}, journal={Veterinary immunology and immunopathology}, author={Crisci, E and Ballester, M and Domínguez, J and Segalés, J and Montoya, M}, year={2010}, month={Aug}, pages={305–310} }
 @article{tarradas_argilaguet_rosell_nofrarías_crisci_córdoba_pérez-martín_díaz_rodríguez_domingo_et al._2010, title={Interferon-gamma induction correlates with protection by DNA vaccine expressing E2 glycoprotein against classical swine fever virus infection in domestic pigs.}, volume={142}, url={http://europepmc.org/abstract/med/19896784}, DOI={10.1016/j.vetmic.2009.09.043}, abstractNote={Classical swine fever (CSF) is a highly contagious viral infection affecting domestic and wild pigs. For classical swine fever virus (CSFV), immunization with plasmids expressing different versions of glycoprotein E2 has proven an effective way to induce protection. Previously, we have also shown that immunization with DNA vaccine expressing glycoprotein E2 (DNA-E2) induced specific T helper cell responses in the absence of neutralizing antibodies. However, the role of T cell responses in protection against CSFV is largely unknown. Here we have extended these studies to deeply characterize the role of T cell responses by a DNA-E2 and their correlation with protection against CSFV infection. Thus, pigs vaccinated with the DNA vaccine induced a strong cellular immune response, characterized by the specific induction IFN-gamma expressing T cells after vaccination without any detectable levels of CSFV neutralizing antibodies. Constant levels of CSFV-specific IFN-gamma producing cells observed from the beginning of the infection until 7 days after challenge in vaccinated animals might contribute to early control of CSFV replication, at least until neutralizing antibodies are developed. Severe clinical signs of the disease, including high titers of viremia, pyrexia and virus spread to different organs, were recorded in the non-vaccinated challenged animals, in comparison to the vaccinated animals where only one animal showed mild clinical signs and a short peak of viremia. Lack of complete protection in this animal correlated with a delay on the induction of neutralizing antibodies, detectable only from day 11 post-CSFV challenge. Conversely, the rest of the pigs within the group developed neutralizing antibodies as early as at day two post-challenge, correlating with sterile protection. Finally, an inverse correlation seemed to exist between early induction of IFN-alpha and the protection observed, while IL-10 seemed to be differentially regulated in vaccinated and non-vaccinated animals. Our results support the relevance of the induction of a strong T cellular response to confer a solid protection upon DNA vaccination against CSFV. Further experiments are needed to be done in order to clarify the key cytokines playing a role in CSFV-protection and to obtain emergency vaccines capable to confer robust and fast protection.}, number={1-2}, journal={Veterinary microbiology}, author={Tarradas, J and Argilaguet, JM and Rosell, R and Nofrarías, M and Crisci, E and Córdoba, L and Pérez-Martín, E and Díaz, I and Rodríguez, F and Domingo, M and et al.}, year={2010}, month={Apr}, pages={51–58} }
 @article{segalés_urniza_alegre_bru_crisci_nofrarías_lópez-soria_balasch_sibila_xu_et al._2009, title={A genetically engineered chimeric vaccine against porcine circovirus type 2 (PCV2) improves clinical, pathological and virological outcomes in postweaning multisystemic wasting syndrome affected farms.}, volume={27}, url={http://europepmc.org/abstract/med/19800439}, DOI={10.1016/j.vaccine.2009.09.084}, abstractNote={The present study describes the effects of a commercially available genetically engineered chimeric vaccine against porcine circovirus type 2 (PCV2) on clinical, pathological and virological features in three multi-site farms suffering from postweaning multisystemic wasting syndrome (PMWS). The vaccine product was able to reduce clinical signs, PCV2 viral load in lymphoid organs and/or sera, and overall mortality in nurseries and fattening units. This is the first time in which is shown that a PCV2 vaccine is able to decrease specifically PMWS-associated mortality. Another novelty of this study is the assessment of PMWS-like histological lesions in a large number of vaccinated and non-vaccinated pigs under field conditions.}, number={52}, author={Segalés, J. and Urniza, A. and Alegre, A. and Bru, T. and Crisci, E. and Nofrarías, M. and López-Soria, S. and Balasch, M. and Sibila, M. and Xu, Z. and et al.}, year={2009}, month={Dec}, pages={7313–7321} }
 @article{crisci_almanza_mena_córdoba_gómez-casado_castón_bárcena_montoya_virology_2009, title={Chimeric calicivirus-like particles elicit protective anti-viral cytotoxic responses without adjuvant.}, volume={387}, url={http://europepmc.org/abstract/med/19327809}, DOI={10.1016/j.virol.2009.02.045}, abstractNote={We have analyzed the potential of virus-like particles (VLPs) from rabbit hemorrhagic disease virus (RHDV) as a delivery system for foreign T cell epitopes. To accomplish this goal, we generated chimeric RHDV-VLPs incorporating a CD8+ T cell epitope (SIINFEKL) derived from chicken ovalbumin (OVA). The OVA epitope was inserted in the capsid protein (VP60) of RHDV at two different locations: 1) the N-terminus, predicted to be facing to the inner core of the VLPs, and 2) a novel insertion site predicted to be located within an exposed loop. Both constructions correctly assembled into VLPs. In vitro, the chimeric VLPs activated dendritic cells for TNF-α secretion and they were processed and presented to specific T cells. In vivo, mice immunized with the chimeric VLPs without adjuvant were able to induce specific cellular responses mediated by cytotoxic and memory T cells. More importantly, immunization with chimeric VLPs was able to resolve an infection by a recombinant vaccinia virus expressing OVA protein.}, number={2}, author={Crisci, E. and Almanza, H. and Mena, I. and Córdoba, L. and Gómez-Casado, E. and Castón, Fraile L., JR and Bárcena, J. and Montoya, M. and Virology}, year={2009}, month={May}, pages={303–312} }
 @article{lorenzoj_elisa_joan_montse_lorenzo_lara_santi_maría_2009, title={Effect of treatment with phytosterols in three herds with porcine respiratory disease complex.}, volume={17}, url={http://europepmc.org/abstract/AGR/IND44168201}, number={1}, journal={Journal of swine health and production}, author={LorenzoJ, Fraile and Elisa, Crisci and Joan, Weenberg and Montse, Armadans and Lorenzo, Mendoza and Lara, Ruiz and Santi, Bernaus and María, Montoya}, year={2009}, month={Jan}, pages={32–41,} }
 @article{grau-roma_crisci_sibila_lópez-soria_nofrarias_cortey_fraile_olvera_segalés_2008, title={A proposal on porcine circovirus type 2 (PCV2) genotype definition and their relation with postweaning multisystemic wasting syndrome (PMWS) occurrence.}, volume={128}, url={http://europepmc.org/abstract/med/17976930}, DOI={10.1016/j.vetmic.2007.09.007}, abstractNote={Porcine circovirus type 2 (PCV2) is the essential infectious agent of postweaning multisystemic wasting syndrome (PMWS). Despite first sequencing studies did not find any association between PCV2 sequences and PMWS occurrence, recent works have suggested the opposite. In the present study, 87 open reading frame 2 (ORF2) sequences obtained from pigs with different clinical conditions and coming from farms with different PMWS status were analyzed. Results further confirmed the existence of two genogroups and the definition of two PCV2 genotypes (1 and 2) is proposed. All sequences included in genotype 1 came from pigs from PMWS affected farms, while all sequences obtained from non-PMWS affected farms corresponded to genotype 2. Moreover, infection of single pigs from PMWS affected farms harbouring both genotypes is described. Present results suggest that PCV2 genotype 1 may potentially be more pathogenic than PCV2 genotype 2.}, number={1-2}, journal={Veterinary microbiology}, author={Grau-Roma, L and Crisci, E and Sibila, M and López-Soria, S and Nofrarias, M and Cortey, M and Fraile, L and Olvera, A and Segalés, J}, year={2008}, month={Apr}, pages={23–35} }
 @inproceedings{fraile_crisci_gimeno_diaz_mateu_montoya_2008, title={IMMUNOMODULATION IN PRRS MLV VACCINATION}, booktitle={20th INTERNATIONAL PIG VETERINARY SOCIETY CONGRESS}, author={Fraile, L and Crisci, E and Gimeno, M and Diaz, I and Mateu, E and Montoya, M}, year={2008}, pages={21} }
 @inproceedings{segalés_urniza_alegre_crisci_pérez_nofrarı́as m_balasch_xu_chu_plana-duran_2008, title={Suvaxyn® Circo ameliorates PCV2-associated lymphoid lesions and PMWS-associated mortality}, booktitle={20th INTERNATIONAL PIG VETERINARY SOCIETY CONGRESS}, author={Segalés, J and Urniza, A and Alegre, A and Crisci, E and Pérez, M and Nofrarı́as M and Balasch, M and Xu, Z and Chu, HJ and Plana-Duran, J}, year={2008}, pages={18} }