@article{fogle_hudson_thomson_sherman_gruen_lacelles_colby_clary_longo_meeker_2021, title={Improved neurocognitive performance in FIV infected cats following treatment with the p75 neurotrophin receptor ligand LM11A-31}, volume={27}, ISSN={["1538-2443"]}, DOI={10.1007/s13365-021-00956-2}, abstractNote={HIV rapidly infects the central nervous system (CNS) and establishes a persistent viral reservoir within microglia, perivascular macrophages and astrocytes. Inefficient control of CNS viral replication by antiretroviral therapy results in chronic inflammation and progressive cognitive decline in up to 50% of infected individuals with no effective treatment options. Neurotrophin based therapies have excellent potential to stabilize and repair the nervous system. A novel non-peptide ligand, LM11A-31, that targets the p75 neurotrophin receptor (p75NTR) has been identified as a small bioavailable molecule capable of strong neuroprotection with minimal side effects. To evaluate the neuroprotective effects of LM11A-31 in a natural infection model, we treated cats chronically infected with feline immunodeficiency virus (FIV) with 13 mg/kg LM11A-31 twice daily over a period of 10 weeks and assessed effects on cognitive functions, open field behaviors, activity, sensory thresholds, plasma FIV, cerebrospinal fluid (CSF) FIV, peripheral blood mononuclear cell provirus, CD4 and CD8 cell counts and general physiology. Between 12 and 18 months post-inoculation, cats began to show signs of neural dysfunction in T maze testing and novel object recognition, which were prevented by LM11A-31 treatment. Anxiety-like behavior was reduced in the open field and no changes were seen in sensory thresholds. Systemic FIV titers were unaffected but treated cats exhibited a log drop in CSF FIV titers. No significant adverse effects were observed under all conditions. The data indicate that LM11A-31 is likely to be a potent adjunctive treatment for the control of neurodegeneration in HIV infected individuals.}, number={2}, journal={JOURNAL OF NEUROVIROLOGY}, author={Fogle, Jonathan E. and Hudson, Lola and Thomson, Andrea and Sherman, Barbara and Gruen, Margaret and Lacelles, B. Duncan and Colby, Brenda M. and Clary, Gillian and Longo, Frank and Meeker, Rick B.}, year={2021}, month={Apr}, pages={302–324} }
 @article{spiri_novacco_meli_stirn_riond_fogle_boretti_herbert_hosie_hofmann-lehmann_2021, title={Modified-Live Feline Calicivirus Vaccination Elicits Cellular Immunity against a Current Feline Calicivirus Field Strain in an Experimental Feline Challenge Study}, volume={13}, ISSN={["1999-4915"]}, DOI={10.3390/v13091736}, abstractNote={Feline calicivirus (FCV) is a common cat virus associated with oral ulcerations and virulent-systemic disease. Efficacious FCV vaccines protect against severe disease but not against infection. The high genetic diversity of FCV poses a challenge in vaccine design. Protection against FCV has been related to humoral and cellular immunity; the latter has not been studied in detail. This study investigates the cellular and humoral immune response of specified pathogen-free (SPF) cats after modified-live FCV F9 vaccinations and two heterologous FCV challenges by the analysis of lymphocyte subsets, cytokine mRNA transcription levels, interferon (IFN)-γ release assays in peripheral blood mononuclear cells (PBMCs), anti-FCV antibodies, and neutralisation activity. Vaccinated cats developed a Th1 cytokine response after vaccination. Vaccination resulted in antibodies with neutralising activity against the vaccine but not the challenge viruses. Remarkably, IFN-γ-releasing PBMCs were detected in vaccinated cats upon stimulation with the vaccine strain and the first heterologous FCV challenge strain. After the first experimental infection, the mRNA transcription levels of perforin, granzyme B, INF-γ, and antiviral factor MX1 and the number of IFN-γ-releasing PBMCs when stimulated with the first challenge virus were higher in vaccinated cats compared to control cats. The first FCV challenge induced crossneutralising antibodies in all cats against the second challenge virus. Before the second challenge, vaccinated cats had a higher number of IFN-γ-releasing PBMCs when stimulated with the second challenge virus than control cats. After the second FCV challenge, there were less significant differences detected between the groups regarding lymphocyte subsets and cytokine mRNA transcription levels. In conclusion, modified-live FCV vaccination induced cellular but not humoral crossimmunity in SPF cats; innate immune mechanisms, secretory and membranolytic pathways, and IFN-γ-releasing PBMCs seem to be important in the host immune defence against FCV.}, number={9}, journal={VIRUSES-BASEL}, author={Spiri, Andrea M. and Novacco, Marilisa and Meli, Marina L. and Stirn, Martina and Riond, Barbara and Fogle, Jonathan E. and Boretti, Felicitas S. and Herbert, Imogen and Hosie, Margaret J. and Hofmann-Lehmann, Regina}, year={2021}, month={Sep} }
 @article{genova_nonnis_maffioli_tedeschi_strillacci_carisetti_sironi_cupaioli_di nanni_mezzelani_et al._2021, title={Multi-omic analyses in Abyssinian cats with primary renal amyloid deposits}, volume={11}, ISSN={2045-2322}, url={http://dx.doi.org/10.1038/s41598-021-87168-0}, DOI={10.1038/s41598-021-87168-0}, abstractNote={Abstract}, number={1}, journal={Scientific Reports}, publisher={Springer Science and Business Media LLC}, author={Genova, Francesca and Nonnis, Simona and Maffioli, Elisa and Tedeschi, Gabriella and Strillacci, Maria Giuseppina and Carisetti, Michela and Sironi, Giuseppe and Cupaioli, Francesca Anna and Di Nanni, Noemi and Mezzelani, Alessandra and et al.}, year={2021}, month={Apr} }
 @article{balko_fogle_stuska_fogle_posner_2021, title={Retrospective and prospective assessment of butorphanol, azaperone and medetomidine (BAM (TM)) for immobilisation of feral horses (Equus ferus caballus)}, volume={7}, ISSN={["2042-3306"]}, DOI={10.1111/evj.13490}, abstractNote={Abstract}, journal={EQUINE VETERINARY JOURNAL}, author={Balko, Julie A. and Fogle, Callie and Stuska, Susan J. and Fogle, Jonathan E. and Posner, Lysa P.}, year={2021}, month={Jul} }
 @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={12}, ISSN={1664-3224}, url={http://dx.doi.org/10.3389/fimmu.2021.637613}, 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}, publisher={Frontiers Media SA}, 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 Käser, Tobias}, year={2021}, month={Mar} }
 @article{mowat_avelino_bowyer_parslow_westermeyer_foster_fogle_bizikova_2020, title={Detection of circulating anti-retinal antibodies in dogs with sudden acquired retinal degeneration syndrome using indirect immunofluorescence: A case control study}, volume={193}, ISSN={["1096-0007"]}, DOI={10.1016/j.exer.2020.107989}, abstractNote={Sudden acquired retinal degeneration syndrome (SARDS) in dogs is proposed to have an immune-mediated etiology. However, there is conflicting evidence regarding the presence of antiretinal antibodies, as assessed by western blotting, in the serum of SARDS patients. Because of the possibility that antibodies recognize only conformational epitopes, we hypothesized that a more sensitive method to investigate circulating retinal autoantibodies in SARDS is immunofluorescence. Sera from 14 dogs with early SARDS, and 14 age- and breed-matched healthy control dogs were screened for circulating antiretinal IgG, IgM, IgE and IgA using indirect immunofluorescence on lightly fixed frozen sections of normal canine retina. Controls without canine serum were also performed. A nuclear counterstain was used to identify cellular retinal layers. Images were obtained using a fluorescence microscope, and 2-3 separate masked observers graded retinal layers for fluorescence staining intensity using a 0–3 scale. Total circulating IgG and IgM was assessed by radial immunodiffusion. Statistical analysis was performed using 2-way ANOVA, paired 2-tailed student's t-test and correlation analysis. Intensity of IgG staining of photoreceptor outer segments was significantly higher using serum from dogs with SARDS compared with healthy controls in 2/3 observers (P < 0.05). Intensity of IgM staining throughout the retina was higher in SARDS dogs compared to matched healthy controls (P < 0.0001), although no specific retinal layer was statistically significant. There were no differences in staining intensity for IgE or IgA. Dogs with SARDS had a comparably lower circulating IgG and higher IgM than healthy controls (P = 0.01 and 0.001 respectively) and IgG and IgM were negatively correlated (r = −0.69, P = 0.007). Despite having decreased serum IgG compared with healthy controls, circulating IgG in dogs with SARDS binds photoreceptor outer segments to a greater extent. Dogs with SARDS have a relatively higher circulating IgM than matched healthy controls. The pathogenic nature of these antibodies is unknown.}, journal={EXPERIMENTAL EYE RESEARCH}, author={Mowat, Freya M. and Avelino, Janelle and Bowyer, Ashley and Parslow, Vanessa and Westermeyer, Hans D. and Foster, Melanie L. and Fogle, Jonathan E. and Bizikova, Petra}, year={2020}, month={Apr} }
 @article{meichner_stokol_tarigo_avery_burkhard_comazzi_fogle_stowe_rütgen_seelig_et al._2020, title={Multicenter flow cytometry proficiency testing of canine blood and lymph node samples}, volume={49}, ISSN={0275-6382}, url={http://dx.doi.org/10.1111/vcp.12843}, DOI={10.1111/vcp.12843}, abstractNote={Abstract}, number={2}, journal={Veterinary Clinical Pathology}, publisher={Wiley}, author={Meichner, Kristina and Stokol, Tracy and Tarigo, Jaime and Avery, Anne and Burkhard, Mary J. and Comazzi, Stefano and Fogle, Jonathan and Stowe, Devorah Marks and Rütgen, Barbara and Seelig, Davis and et al.}, year={2020}, month={Apr}, pages={249–257} }
 @article{garden_kidd_mexas_chang_jeffery_blois_fogle_macneill_lubas_birkenheuer_et al._2019, title={ACVIM consensus statement on the diagnosis of immune-mediated hemolytic anemia in dogs and cats}, volume={33}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.15441}, abstractNote={Immune‐mediated hemolytic anemia (IMHA) is an important cause of morbidity and mortality in dogs. IMHA also occurs in cats, although less commonly. IMHA is considered secondary when it can be attributed to an underlying disease, and as primary (idiopathic) if no cause is found. Eliminating diseases that cause IMHA may attenuate or stop immune‐mediated erythrocyte destruction, and adverse consequences of long‐term immunosuppressive treatment can be avoided. Infections, cancer, drugs, vaccines, and inflammatory processes may be underlying causes of IMHA. Evidence for these comorbidities has not been systematically evaluated, rendering evidence‐based decisions difficult. We identified and extracted data from studies published in the veterinary literature and developed a novel tool for evaluation of evidence quality, using it to assess study design, diagnostic criteria for IMHA, comorbidities, and causality. Succinct evidence summary statements were written, along with screening recommendations. Statements were refined by conducting 3 iterations of Delphi review with panel and task force members. Commentary was solicited from several professional bodies to maximize clinical applicability before the recommendations were submitted. The resulting document is intended to provide clinical guidelines for diagnosis of, and underlying disease screening for, IMHA in dogs and cats. These should be implemented with consideration of animal, owner, and geographical factors.}, number={2}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Garden, Oliver A. and Kidd, Linda and Mexas, Angela M. and Chang, Yu-Mei and Jeffery, Unity and Blois, Shauna L. and Fogle, Jonathan E. and MacNeill, Amy L. and Lubas, George and Birkenheuer, Adam and et al.}, year={2019}, pages={313–334} }
 @book{fogle_2019, edition={4th}, title={Juvenile polyarteritis}, journal={Clinical Veterinary Advisor}, publisher={Elsevier}, author={Fogle, JE}, year={2019} }
 @inbook{fogle_2019, edition={4th}, title={Neonatal Isoerythrolysis}, booktitle={Clinical Veterinary Advisor}, publisher={Elsevier}, author={Fogle, JE}, year={2019} }
 @article{ontiveros_ueda_harris_stern_lyons_gandolfi_aberdein_garrick_munday_alves_et al._2019, title={Precision medicine validation: identifying the MYBPC3 A31P variant with whole-genome sequencing in two Maine Coon cats with hypertrophic cardiomyopathy}, volume={21}, ISSN={["1532-2750"]}, DOI={10.1177/1098612X18816460}, abstractNote={Objectives The objective of this study was to perform a proof-of-concept experiment that validates a precision medicine approach to identify variants associated with hypertrophic cardiomyopathy (HCM). We hypothesized that whole-genome sequencing would identify variant(s) associated with HCM in two affected Maine Coon/Maine Coon cross cats when compared with 79 controls of various breeds. }, number={12}, journal={JOURNAL OF FELINE MEDICINE AND SURGERY}, author={Ontiveros, Eric S. and Ueda, Yu and Harris, Samantha P. and Stern, Joshua A. and Lyons, Leslie A. and Gandolfi, Barbara and Aberdein, Danielle and Garrick, Dorian J. and Munday, John S. and Alves, Paulo C. and et al.}, year={2019}, month={Dec}, pages={1086–1093} }
 @article{kennedy_thomson_griffith_fogle_lascelles_meeker_sherman_gruen_2018, title={Enrichment Preferences of FIV-Infected and Uninfected Laboratory-Housed Cats}, volume={10}, ISSN={1999-4915}, url={http://dx.doi.org/10.3390/v10070353}, DOI={10.3390/v10070353}, abstractNote={Environmental enrichment is critical for alleviating stress in laboratory felines. However, there is a paucity of information about suitable enrichment for cats. This study aimed to determine preferred enrichment options of individually-housed, castrated male domestic short hair cats (Felis catus) used in a longitudinal study of the effects of chronic feline immunodeficiency virus (FIV) infection, and to determine if the FIV status of the cats affected enrichment preferences. Preference testing was performed with two types of grooming brushes, three different interactive play options, including a laser, ball, and petting interaction with a familiar investigator, and two types of toenail conditioning objects. We found that cats elected to be brushed, preferred social interaction and play with the laser to the ball, and preferred to scratch on an inclined-box toenail conditioning object compared to a horizontal, circular toenail conditioning object. There were individual preferences for enrichment opportunities. There were no differences in preferences between FIV-infected and sham-infected cats. These enrichment preferences may be used to advise laboratory animal facilities and researchers about how to best accommodate the behavioral needs of laboratory cats.}, number={7}, journal={Viruses}, publisher={MDPI AG}, author={Kennedy, Claudia and Thomson, Andrea and Griffith, Emily and Fogle, Jonathan and Lascelles, B. and Meeker, Rick and Sherman, Barbara and Gruen, Margaret}, year={2018}, month={Jul}, pages={353} }
 @misc{nag_de paris_fogle_2018, title={Epigenetic Modulation of CD8(+) T Cell Function in Lentivirus Infections: A Review}, volume={10}, ISSN={["1999-4915"]}, DOI={10.3390/v10050227}, abstractNote={CD8+ T cells are critical for controlling viremia during human immunodeficiency virus (HIV) infection. These cells produce cytolytic factors and antiviral cytokines that eliminate virally- infected cells. During the chronic phase of HIV infection, CD8+ T cells progressively lose their proliferative capacity and antiviral functions. These dysfunctional cells are unable to clear the productively infected and reactivated cells, representing a roadblock in HIV cure. Therefore, mechanisms to understand CD8+ T cell dysfunction and strategies to boost CD8+ T cell function need to be investigated. Using the feline immunodeficiency virus (FIV) model for lentiviral persistence, we have demonstrated that CD8+ T cells exhibit epigenetic changes such as DNA demethylation during the course of infection as compared to uninfected cats. We have also demonstrated that lentivirus-activated CD4+CD25+ T regulatory cells induce forkhead box P3 (Foxp3) expression in virus-specific CD8+ T cell targets, which binds the interleukin (IL)-2, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ promoters in these CD8+ T cells. Finally, we have reported that epigenetic modulation reduces Foxp3 binding to these promoter regions. This review compares and contrasts our current understanding of CD8+ T cell epigenetics and mechanisms of lymphocyte suppression during the course of lentiviral infection for two animal models, FIV and simian immunodeficiency virus (SIV).}, number={5}, journal={VIRUSES-BASEL}, author={Nag, Mukta and De Paris, Kristina and Fogle, Jonathan E.}, year={2018}, month={May} }
 @article{nag_wang_de paris_fogle_2018, title={Histone Modulation Blocks Treg-Induced Foxp3 Binding to the IL-2 Promoter of Virus-Specific CD8(+) T Cells from Feline Immunodeficiency Virus-Infected Cats}, volume={10}, ISSN={["1999-4915"]}, DOI={10.3390/v10060287}, abstractNote={CD8+ T cells are critical for controlling HIV infection. During the chronic phase of lentiviral infection, CD8+ T cells lose their proliferative capacity and exhibit impaired antiviral function. This loss of CD8+ T cell function is due, in part, to CD4+CD25+ T regulatory (Treg) cell-mediated suppression. Our research group has demonstrated that lentivirus-activated CD4+CD25+ Treg cells induce the repressive transcription factor forkhead box P3 (Foxp3) in autologous CD8+ T cells following co-culture. We have recently reported that Treg-induced Foxp3 binds the interleukin-2 (IL-2), interferon-γ (IFN- γ), and tumor necrosis factor-α (TNF-α) promoters in virus-specific CD8+ T cells. These data suggest an important role of Foxp3-mediated CD8+ T cell dysfunction in lentiviral infection. To elucidate the mechanism of this suppression, we previously reported that decreased methylation facilitates Foxp3 binding in mitogen-activated CD8+ T cells from feline immunodeficiency virus (FIV)-infected cats. We demonstrated the reduced binding of Foxp3 to the IL-2 promoter by increasing methylation of CD8+ T cells. In the studies presented here, we ask if another form of epigenetic modulation might alleviate Foxp3-mediated suppression in CD8+ T cells. We hypothesized that decreasing histone acetylation in virus-specific CD8+ T cells would decrease Treg-induced Foxp3 binding to the IL-2 promoter. Indeed, using anacardic acid (AA), a known histone acetyl transferase (HAT) inhibitor, we demonstrate a reduction in Foxp3 binding to the IL-2 promoter in virus-specific CD8+ T cells co-cultured with autologous Treg cells. These data identify a novel mechanism of Foxp3-mediated CD8+ T cell dysfunction during lentiviral infection.}, number={6}, journal={VIRUSES-BASEL}, author={Nag, Mukta and Wang, Yan and De Paris, Kristina and Fogle, Jonathan E.}, year={2018}, month={Jun} }
 @article{wang_nag_tuohy_de paris_fogle_2018, title={T Regulatory Cell Induced Foxp3 Binds the IL2, IFNγ, and TNFα Promoters in Virus-Specific CD8+ T Cells from Feline Immunodeficiency Virus Infected Cats}, volume={34}, ISSN={0889-2229 1931-8405}, url={http://dx.doi.org/10.1089/aid.2017.0187}, DOI={10.1089/aid.2017.0187}, abstractNote={Polyfunctional CD8+ T cells play a critical role in controlling viremia during AIDS lentiviral infections. However, for most HIV-infected individuals, virus-specific CD8+ T cells exhibit loss of polyfunctionality, including loss of IL2, TNFα, and IFNγ. Using the feline immunodeficiency virus (FIV) model for AIDS lentiviral persistence, our laboratory has demonstrated that FIV-activated Treg cells target CD8+ T cells, leading to a reduction in IL2 and IFNγ production. Furthermore, we have demonstrated that Treg cells induce expression of the repressive transcription factor, Foxp3, in CD8+ T cells. Based upon these findings, we asked if Treg-induced Foxp3 could bind to the IL2, TNFα, and IFNγ promoter regions in virus-specific CD8+ T cells. Following coculture with autologous Treg cells, we demonstrated decreased mRNA levels of IL2 and IFNγ at weeks 4 and 8 postinfection and decreased TNFα at week 4 postinfection in virus-specific CD8+ T cells. We also clearly demonstrated Treg cell-induced Foxp3 expression in virus-specific CD8+ T cells at weeks 1, 4, and 8 postinfection. Finally, we documented Foxp3 binding to the IL2, TNFα, and IFNγ promoters at 8 weeks and 6 months postinfection in virus-specific CD8+ T cells following Treg cell coculture. In summary, the results here clearly demonstrate that Foxp3 inhibits IL2, TNFα, and IFNγ transcription by binding to their promoter regions in lentivirus-specific CD8+ T cells. We believe this is the first description of this process during the course of AIDS lentiviral infection.}, number={3}, journal={AIDS Research and Human Retroviruses}, publisher={Mary Ann Liebert Inc}, author={Wang, Yan and Nag, Mukta and Tuohy, Joanne L. and De Paris, Kristina and Fogle, Jonathan E.}, year={2018}, month={Mar}, pages={269–276} }
 @article{wang_nag_tuohy_fogle_2017, title={Micro-RNA 10a Is Increased in Feline T Regulatory Cells and Increases Foxp3 Protein Expression Following In Vitro Transfection}, volume={4}, ISSN={2306-7381}, url={http://dx.doi.org/10.3390/vetsci4010012}, DOI={10.3390/vetsci4010012}, abstractNote={CD4+CD25+Foxp3+ T regulatory (Treg) cells are activated during the course of lentiviral infection and exhibit heightened suppressor function when compared to Treg cells from uninfected controls. Foxp3 is essential to Treg cell function and multiple studies have documented that lentivirus-activated Treg cells exhibit heightened Foxp3 expression when compared to Treg cells from uninfected controls. Our hypothesis was that lentivirus-induced micro-RNAs (miRNAs) contribute to heightened Treg cell suppressor function by stabilizing Foxp3 expression. We demonstrated that CD4+CD25+ T cells from both feline immunodeficiency virus infected (FIV+) cats and uninfected control cats exhibit increased miRNA 10a and 21 levels compared to autologous CD4+CD25− T cells but there was no difference in the levels of these miRNAs when Treg cells from FIV+ cats were compared to Treg cells from uninfected controls. Further, there was no increase in Foxp3 mRNA following transfection of miRNA 10a or 21 into a feline cell line. However, transfection with miRNA 10a resulted in increased Foxp3 protein expression.}, number={4}, journal={Veterinary Sciences}, publisher={MDPI AG}, author={Wang, Yan and Nag, Mukta and Tuohy, Joanne and Fogle, Jonathan}, year={2017}, month={Feb}, pages={12} }
 @article{tuohy_lascelles_griffith_fogle_2016, title={Association of Canine Osteosarcoma and Monocyte Phenotype and Chemotactic Function}, volume={30}, ISSN={0891-6640}, url={http://dx.doi.org/10.1111/jvim.13983}, DOI={10.1111/jvim.13983}, abstractNote={BackgroundMonocytes/macrophages are likely key cells in immune modulation in dogs with osteosarcoma (OSA). Increased peripheral monocyte counts are negatively correlated with shorter disease‐free intervals in dogs with OSA. Understanding the monocyte/macrophage's modulatory role in dogs with OSA can direct further studies in immunotherapy development for OSA.}, number={4}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Tuohy, J.L. and Lascelles, B.D.X. and Griffith, E.H. and Fogle, J.E.}, year={2016}, month={Jun}, pages={1167–1178} }
 @article{fogle_jacob_blikslager_edwards_wagner_dean_fogle_2016, title={Comparison of lipopolysaccharides and soluble CD14 measurement between clinically endotoxaemic and nonendotoxaemic horses}, volume={49}, ISSN={0425-1644}, url={http://dx.doi.org/10.1111/evj.12582}, DOI={10.1111/evj.12582}, abstractNote={Summary}, number={2}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Fogle, J. and Jacob, M. and Blikslager, A. and Edwards, A. and Wagner, B. and Dean, K. and Fogle, C.}, year={2016}, month={May}, pages={155–159} }
 @article{faiz_cortes_guy_fogle_gimeno_2016, title={Efficacy of various Marek's disease vaccines protocols for prevention of Marek's disease virus-induced immunosuppression}, volume={34}, ISSN={["1873-2518"]}, DOI={10.1016/j.vaccine.2016.06.061}, abstractNote={Marek’s disease virus (MDV) induces tumors and severe immunosuppression in chickens. MDV-induced immunosuppression (MDV-IS) is very complex and difficult to study. In particular, the late MDV-IS (late-MDV-IS) is of great concern since it can occur in the absence of lymphoid organ atrophy or gross tumors. We have recently developed a model to reproduce late-MDV-IS under laboratory conditions. This model measures MDV-IS indirectly by assessing the effect of MDV infection on the efficacy of infectious laryngotracheitis (ILT) vaccination; hence the name late-MDV-IS ILT model. In this study, we have used the late-MDV-IS ILT model to evaluate if MD vaccination can protect against late-MDV-IS. One experiment was conducted to determine whether serotype 1 MD vaccines (CVI988 and Md5ΔMEQ) could induce late-MDV-IS by themselves. Three additional experiments were conducted to evaluate efficacy of different MD vaccines (HVT, HVT+SB-1, CVI988, and Md5ΔMEQ) and different vaccine protocols (day-old vaccination, in ovo vaccination, and double vaccination) against late-MDV-IS. Our results show that none of the currently used vaccine protocols (HVT, HVT+SB-1, or CVI988 administered at day of age, in ovo, or in double vaccination protocols) protected against late-MDV-IS induced by vv+MDV strains 648A and 686. Experimental vaccine Md5ΔMEQ administered subcutaneously at one day of age was the only vaccine protocol that significantly reduced late-MDV-IS induced by vv+MDV strain 686. This study demonstrates that currently used vaccine protocols confer high levels of protection against MDV-induced tumors (protection index = 100), but do not protect against late-MDV-IS; thus, commercial poultry flocks could suffer late-MDV-IS even in complete absence of tumors. Our results suggest that MDV-IS might not be related to the development of tumors and novel control methods are needed. Further evaluation of the experimental vaccine Md5ΔMEQ might shed light on protective mechanisms against late-MDV-IS.}, number={35}, journal={VACCINE}, author={Faiz, Nik M. and Cortes, Aneg L. and Guy, James S. and Fogle, Jonathan E. and Gimeno, Isabel M.}, year={2016}, month={Jul}, pages={4180–4187} }
 @article{meichner_fogle_english_suter_2016, title={Expression of Apoptosis-regulating Proteins Bcl-2 and Bax in Lymph Node Aspirates from Dogs with Lymphoma}, volume={30}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.13937}, abstractNote={BackgroundDysregulated apoptosis is a hallmark of tumorigenesis, and is also involved in resistance to cytotoxic treatment, and might be relevant in lymphoma in dogs.}, number={3}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Meichner, K. and Fogle, J. E. and English, L. and Suter, S. E.}, year={2016}, pages={819–826} }
 @article{meichner_kraszeski_durrant_grindem_breuhaus_moore_neel_linder_borst_fogle_et al._2016, title={Extreme lymphocytosis with myelomonocytic morphology in a horse with diffuse large B-cell lymphoma}, volume={46}, ISSN={0275-6382}, url={http://dx.doi.org/10.1111/vcp.12435}, DOI={10.1111/vcp.12435}, abstractNote={Abstract}, number={1}, journal={Veterinary Clinical Pathology}, publisher={Wiley}, author={Meichner, Kristina and Kraszeski, Blaire H. and Durrant, Jessica R. and Grindem, Carol B. and Breuhaus, Babetta A. and Moore, Peter F. and Neel, Jennifer A. and Linder, Keith E. and Borst, Luke B. and Fogle, Jonathan E. and et al.}, year={2016}, month={Dec}, pages={64–71} }
 @article{fogle_tarigo_thalheim_williams_english_suter_2015, title={CD45+ and CD45− lymphocyte populations identified by flow cytometry from dogs with lymphoma exhibit similar morphology and the same clonal (B cell or T cell) lineage}, volume={168}, ISSN={0165-2427}, url={http://dx.doi.org/10.1016/j.vetimm.2015.10.004}, DOI={10.1016/j.vetimm.2015.10.004}, abstractNote={Flow cytometric analysis of canine lymphoma sometimes demonstrates a mixed population of CD45+ and CD45- lymphocytes. Recently, indolent forms of canine lymphoma have been described which are associated with the loss of CD45 expression, warranting further investigation of the role of CD45 in canine lymphoma. The purpose of this study was to compare morphology and assess clonal origin between CD45+ and CD45- lymphocyte populations identified by flow cytometry in confirmed cases of canine B- and T-cell lymphoma. Our hypothesis was that the CD45- population of lymphocytes represented a phenotypic variant of the CD45+ population. Fifteen client-owned dogs with lymphoma and distinct CD45+ and CD45- lymphocyte populations identified by flow cytometry were identified for a blinded, prospective assessment of morphology and clonal origin (B cell or T cell) between populations of sorted CD45+ and CD45- cells. Lymphocytes were isolated from 11 dogs for paired cytologic evaluation. In 10/11 dogs, the CD45+ and CD45- samples were similar (95% C.I., 0.301-1.00). DNA was harvested from sorted populations of CD45+ and CD45- cells from 12/15 dogs and PARR analysis produced amplicons of identical size from both populations, indicating that 100% (12/12) were of the same lineage, B cell or T cell (95% C.I., 0.757-1.00). Collectively, our data suggests that the CD45- population identified in dogs with lymphoma represents a phenotypic variant of the CD45+ population.}, number={3-4}, journal={Veterinary Immunology and Immunopathology}, publisher={Elsevier BV}, author={Fogle, J.E. and Tarigo, J.L. and Thalheim, L. and Williams, L.E. and English, L.B. and Suter, S.E.}, year={2015}, month={Dec}, pages={242–248} }
 @article{hood_thompson_akaronu_miller_fogle_2015, title={Monocyte-Derived Dendritic Cells from Feline Immunodeficiency Virus Positive Cats are Productively Infected and Maintain CD8+ T Cell Stimulatory Capacity}, volume={2}, ISSN={2469-567X}, url={http://dx.doi.org/10.23937/2469-567x/1510007}, DOI={10.23937/2469-567x/1510007}, abstractNote={Dendritic cells (DCs) have been utilized to enhance CD8+ T cell responses to pathogen-associated peptides for enhancement of vaccine efficacy. CD8+ T cells play a central role in the elimination of viruses during acute viral infection and control of viremia during chronic viral infection. For lentiviral infections such as HIV and FIV, dendritic cell vaccines may be useful for augmenting CD8+ T cell function. Therefore, we asked if monocyte-derived dendritic cells (moDCs) from FIV+ chronically infected cats maintained the ability to stimulate CD8+ T cells in the absence of exogenous antigen, when compared to uninfected controls. Using high speed cell sorting, monocytes were isolated from PBMCs based on forward versus side scatter gating. Cells were then cultured with IL-4 and GM-CSF over the course of 6 days, and LPS was added to stimulate maturation after the first 72 hours. We confirmed the identity and maturation status of cells by cytologic examination and FITC-dextran uptake. We then assessed differences in CD8+ T cell proliferation in the presence of monocytes / macrophages (M/M), immature dendritic cells (iDCs), and mature dendritic cells (mDCs). We demonstrated that CD8+ T cell proliferation is maintained in the presence of DCs from FIV+ cats and that production of inflammatory cytokines and chemokines by DCs from FIV+ cats is retained in vitro. Further, we confirmed the presence of virus in co-culture. These results suggest that moDCs from FIV-infected animals serve as viral reservoirs. More importantly, these results support our hypothesis that moDCs maintain the ability to stimulate CD8+ T cells during chronic lentiviral infection.}, number={1}, journal={International Journal of Virology and AIDS}, publisher={ClinMed International Library}, author={Hood, S.F. and Thompson, E.M. and Akaronu, N.O. and Miller, M.M. and Fogle, J.E.}, year={2015}, month={Apr} }
 @article{long_williams_savage_fogle_meeker_hudson_2015, title={Probable primary polydipsia in a domestic shorthair cat}, volume={1}, ISSN={2055-1169 2055-1169}, url={http://dx.doi.org/10.1177/2055116915615370}, DOI={10.1177/2055116915615370}, abstractNote={Case summary A 10-month-old neutered male domestic shorthair cat presented with a 4 month history of polyuria and polydipsia. After a thorough diagnostic work-up the only abnormal findings were hyposthenuria and an elevated random plasma osmolality level. Trial therapy with the oral and ophthalmic forms of desmopressin failed to concentrate urine. A modified water deprivation test confirmed the ability to concentrate urine above a urine specific gravity (USG) of 1.035. After transitioning the cat to a higher sodium diet and instituting several enrichment changes to the cat’s environment, average water consumption and urine output levels decreased to almost normal levels and USG increased from 1.006 to 1.022. These findings provide strong evidence that primary polydipsia was the underlying etiology of the cat’s condition. }, number={2}, journal={Journal of Feline Medicine and Surgery Open Reports}, publisher={SAGE Publications}, author={Long, Charles Tyler and Williams, Morika and Savage, Mason and Fogle, Jonathan and Meeker, Rick and Hudson, Lola}, year={2015}, month={Jul}, pages={205511691561537} }
 @article{miller_petty_tompkins_fogle_2014, title={CD4+CD25+ T regulatory cells activated during feline immunodeficiency virus infection convert T helper cells into functional suppressors through a membrane-bound TGFβ / GARP-mediated mechanism}, volume={11}, ISSN={1743-422X}, url={http://dx.doi.org/10.1186/1743-422X-11-7}, DOI={10.1186/1743-422x-11-7}, abstractNote={We and others have previously reported that cell membrane-bound TGFβ (mTGFβ) on activated T regulatory (Treg) cells mediates suppressor function. Current findings suggest that a novel protein known as Glycoprotein A Repetitions Predominant (GARP) anchors mTGFβ to the Treg cell surface and facilitates suppressor activity. Recently, we have described that GARP+TGFβ+ Treg cells expand during the course of FIV infection. Because Treg cells are anergic and generally exhibit poor proliferative ability, we asked how Treg homeostasis is maintained during the course of feline immunodeficiency virus (FIV) infection. Here, we report that Treg cells from FIV+ cats express GARP and mTGFβ and convert T helper (Th) cells into phenotypic and functional Treg cells. Th to Treg conversion was abrogated by anti-TGFβ or anti-GARP treatment of Treg cells or by anti-TGFβRII treatment of Th cells, suggesting that Treg cell recruitment from the Th pool is mediated by TGFβ/TGFβRII signaling and that cell-surface GARP plays a major role in this process. These findings suggest Th to Treg conversion may initiate a cascade of events that contributes to the maintenance of virus reservoirs, progressive Th cell immunosuppression, and the development of immunodeficiency, all of which are central to the pathogenesis of AIDS lentivirus infections.}, number={1}, journal={Virology Journal}, publisher={Springer Nature}, author={Miller, Michelle M and Petty, Christopher S and Tompkins, Mary B and Fogle, Jonathan E}, year={2014}, pages={7} }
 @article{meng_tompkins_miller_fogle_2014, title={Lentivirus-Activated T Regulatory Cells Suppress T Helper Cell Interleukin-2 Production by Inhibiting Nuclear Factor of Activated T Cells 2 Binding to the Interleukin-2 Promoter}, volume={30}, ISSN={["1931-8405"]}, DOI={10.1089/aid.2013.0062}, abstractNote={Using the feline immunodeficiency virus (FIV) model for AIDS lentivirus infection, we previously demonstrated that Treg cells from FIV-infected cats up-regulate membrane-associated tumor growth factor beta (mTGF-ß) during the course of infection and that activated T lymphocytes up-regulate TGF-ß receptor II (TGF-ßRII) during the course of infection. Furthermore, we have demonstrated that autologous coculture of Tregs with Th cells from FIV-infected cats leads to suppression of interleukin (IL)-2 production and loss of proliferation in a TGF-ß-dependent fashion. Nuclear factor of activated T cells (NFAT) 2 has been identified as integral to effector Th cell maturation and function by promoting IL-2 transcription. Therefore, we questioned whether NFAT2 expression might be altered by TGF-β signaling. Feline NFAT2 exon sequences were identified based upon sequence homology to human and murine NFAT2. Following stimulation, IL-2 and NFAT2 mRNA levels were similarly increased in both FIV(-) and FIV(+) cats. Activated CD4(+)CD25(-) cells from both FIV(-) and FIV(+) cats cocultured with autologous CD4(+)CD25(+) cells or treated with TGF-β demonstrated decreased IL-2 production; however, NFAT2 mRNA levels were unaffected. Although NFAT2 mRNA levels were unaffected, chromatin immunoprecipitation (ChIP) for NFAT2 indicated decreased NFAT2 binding at the IL-2 promoter in suppressed Th cells. These data suggest that TGF-β-mediated Treg cell suppression of IL-2 transcription is modulated through alterations in NFAT2 binding to the IL-2 promoter.}, number={1}, journal={AIDS RESEARCH AND HUMAN RETROVIRUSES}, author={Meng, Liping and Tompkins, Mary and Miller, Michelle and Fogle, Jonathan}, year={2014}, month={Jan}, pages={58–66} }
 @article{miller_akaronu_thompson_hood_fogle_2014, title={Modulating DNA Methylation in Activated CD8+ T Cells Inhibits Regulatory T Cell–Induced Binding of Foxp3 to the CD8+ T Cell IL-2 Promoter}, volume={194}, ISSN={0022-1767 1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.1401762}, DOI={10.4049/jimmunol.1401762}, abstractNote={Abstract}, number={3}, journal={The Journal of Immunology}, publisher={The American Association of Immunologists}, author={Miller, Michelle M. and Akaronu, Nnenna and Thompson, Elizabeth M. and Hood, Sylvia F. and Fogle, Jonathan E.}, year={2014}, month={Dec}, pages={990–998} }
 @article{miller_thompson_suter_fogle_2013, title={CD8+ clonality is associated with prolonged acute plasma viremia and altered mRNA cytokine profiles during the course of Feline Immunodeficiency Virus infection}, volume={152}, ISSN={0165-2427}, url={http://dx.doi.org/10.1016/j.vetimm.2012.12.005}, DOI={10.1016/j.vetimm.2012.12.005}, abstractNote={Acute lentiviral infection is characterized by early CD8(+) cytotoxic T cell (CTL) activity and a subsequent decline in plasma viremia. However, CD8(+) lymphocytes fail to eliminate the virus and a progressive T cell immune dysfunction develops during the course of chronic lentiviral infection. To further define this CD8(+) immune dysfunction we utilized PARR (PCR for antigen receptor rearrangements), a technique which measures clonally expanded lymphocyte populations by comparison of highly conserved T cell receptor (TCR) regions to identify the prevalence of clonal CD8(+) T cells following FIV infection. We then compared phenotype, mRNA profiles, CD8(+) proliferation and plasma viremia during acute and chronic infection for PARR positive (PARR(+)) and PARR negative (PARR(-)) Feline Immunodeficiency Virus (FIV) infected cats. We demonstrated that approximately forty percent of the FIV(+) cats examined exhibit CD8(+) clonality compared to none of the FIV(-) control cats. There were no phenotypic differences between PARR(+) and PARR(-) CD8(+) lymphocytes from FIV(+) cats but retrospective analysis of plasma viremia over the course of infection revealed a delayed peak in plasma viremia and a decline in lymphocyte counts were observed in the PARR(+) group during acute infection. CD8(+) lymphocytes isolated from chronically infected PARR(-) cats exhibited significantly higher mRNA expression of IFN-γ and IL-2 following mitogenic stimulation when compared to PARR(+) CD8(+) lymphocytes. These data suggest that clonal CD8(+) expansion may be related to impaired control of acute viremia and less effective CD8(+) anti-viral function. Using PARR to assess changes in CD8(+) clonality during the progression from acute to chronic FIV infection may help to better characterize the factors which contribute to CD8(+) anergy and lentiviral persistence.}, number={3-4}, journal={Veterinary Immunology and Immunopathology}, publisher={Elsevier BV}, author={Miller, Michelle M. and Thompson, Elizabeth M. and Suter, Steven E. and Fogle, Jonathan E.}, year={2013}, month={Apr}, pages={200–208} }
 @article{miller_fogle_ross_tompkins_2013, title={Feline Glycoprotein A Repetitions Predominant Anchors Transforming Growth Factor Beta on the Surface of Activated CD4(+)CD25(+) Regulatory T Cells and Mediates AIDS Lentivirus-Induced T Cell Immunodeficiency}, volume={29}, ISSN={["1931-8405"]}, DOI={10.1089/aid.2012.0322}, abstractNote={Using the feline immunodeficiency virus (FIV) model for AIDS-lentivirus infection, our laboratory has previously demonstrated that T regulatory (Treg) cell-mediated immune T and B cell dysfunction contributes to lentivirus persistence and chronic disease through membrane bound transforming growth factor beta (mTGFb). Studying Treg cells in the context of infection has been problematic as no inducible marker for activated Treg cells had been identified. However, recent reports in human Treg studies have described a novel protein, glycoprotein A repetitions predominant (GARP), as a unique marker of activated human Treg cells that anchors mTGFb. Herein we extend these studies to the feline Treg system, identifying feline GARP and demonstrating that human and feline GARP proteins are homologous in structure, expression pattern, and ability to form a complex with TGFb. We further demonstrate that GARP and TGFb form a complex on the surface of activated Treg cells and that these GARP(+)TGFb(+) Treg cells are highly efficient suppressor cells. Analysis of expression of this Treg activation marker in the FIV-AIDS model reveals an up-regulation of GARP expressing Treg cells during chronic FIV infection. We demonstrate that the GARP(+) Treg cells from FIV-infected cats suppress T helper cells in vivo and that blocking GARP or TGFb eliminates this suppression. These data suggest that GARP is expressed in complex with TGFb on the surface of activated Treg cells and plays an important role in TGFb(+) Treg-mediated T cell immune suppression during lentivirus infection.}, number={4}, journal={AIDS RESEARCH AND HUMAN RETROVIRUSES}, author={Miller, Michelle M. and Fogle, Jonathan E. and Ross, Peter and Tompkins, Mary B.}, year={2013}, month={Apr}, pages={641–651} }
 @article{sibley_miller_fogle_2013, title={Human intravenous immunoglobulin (hIVIG) inhibits anti-CD32 antibody binding to canine DH82 cells and canine monocytes in vitro}, volume={151}, ISSN={["0165-2427"]}, DOI={10.1016/j.vetimm.2012.11.013}, abstractNote={The IgG receptors CD16 and CD32 (Fc(γ)RIII and Fc(γ)RII) link the humoral immune response to effector cell immune responses by binding immune complexes. Human intravenous immunoglobulin (hIVIG) consisting of immunoglobulin from pooled donors is reported to block Fc(γ)Rs and has been used to treat a variety of canine autoimmune disorders. Fc(γ)Rs have been poorly described for canine monocytes; therefore, the objectives of this study were to: (1) identify canine monocyte/macrophage Fc(γ)R (CD16 and CD32) expression and (2) demonstrate in vitro hIVIG binding to these receptors. The canine monocyte/macrophage-like cell line (DH82) and monocytes isolated from peripheral blood of healthy dogs were evaluated by flow cytometry (FACS) for CD16 and CD32 expression using commercially available anti-CD16 and anti-CD32 antibodies directed against the human isoforms. The mean percentage of cells expressing CD16 was 55% of DH82 cells and 13% of blood monocytes and the mean percentage of cells expressing CD32 was 85% of DH82 cells and 73% of blood monocytes. Immunoprecipitation of canine DH82 cells lysate using the same anti-CD16 or anti-CD32 antibodies suggested that these anti-human antibodies recognize the canine homologues. To demonstrate Fc(γ)R blockade, cells were incubated with increasing concentrations of hIVIG and then incubated with anti-CD16 or anti-CD32 antibodies. The percentage of CD32 expression decreased in a concentration dependent fashion in DH82 cells and blood monocytes after incubation with increasing concentrations of IVIG, suggesting that hIVIG was binding to CD32 and inhibiting anti-CD32 antibody binding. The same results were not demonstrated with anti-CD16 antibody. We believe this is the first report to demonstrate Fc(γ) receptors CD16 and CD32 expression on canine monocytes and in vitro CD32 binding by human IgG, which may represent one of the immunomodulatory mechanisms of hIVIG.}, number={3-4}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Sibley, Taryn A. and Miller, Michelle M. and Fogle, Jonathan E.}, year={2013}, month={Feb}, pages={229–234} }
 @article{miller_fogle_tompkins_2013, title={Infection with Feline Immunodeficiency Virus Directly Activates CD4+ CD25+ T Regulatory Cells}, volume={87}, ISSN={0022-538X}, url={http://dx.doi.org/10.1128/JVI.00996-13}, DOI={10.1128/jvi.00996-13}, abstractNote={ABSTRACT}, number={16}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Miller, M. M. and Fogle, J. E. and Tompkins, M. B.}, year={2013}, month={Jun}, pages={9373–9378} }
 @article{thalheim_williams_borst_fogle_suter_2013, title={Lymphoma Immunophenotype of Dogs Determined by Immunohistochemistry, Flow Cytometry, and Polymerase Chain Reaction for Antigen Receptor Rearrangements}, volume={27}, ISSN={0891-6640}, url={http://dx.doi.org/10.1111/jvim.12185}, DOI={10.1111/jvim.12185}, abstractNote={BackgroundImmunohistochemistry (IHC), flow cytometry (FC), and PCR for antigen receptor rearrangements (PARR) are 3 widely utilized tests to determine immunophenotype in dogs with lymphoma (LSA).}, number={6}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Thalheim, L. and Williams, L.E. and Borst, L.B. and Fogle, J.E. and Suter, S.E.}, year={2013}, month={Sep}, pages={1509–1516} }
 @article{miller_fogle_2012, title={Administration of Fozivudine Tidoxil as a Single-Agent Therapeutic during Acute Feline Immunodeficiency Virus Infection Does Not Alter Chronic Infection}, volume={4}, ISSN={1999-4915}, url={http://dx.doi.org/10.3390/v4060954}, DOI={10.3390/v4060954}, abstractNote={Initiating combination antiretroviral therapy (ART) during acute HIV infection has been correlated with decreased viral set point and improved lymphocyte function. However, the long term effects of single-agent therapy administered only during the acute stage of infection (interrupted treatment) remain largely uncharacterized. In this study we provide longitudinal data using the feline immunodeficiency virus (FIV) model for HIV infection. Infected cats were treated with a prophylactic single-agent therapy, Fozivudine tidoxil (FZD), for six weeks, starting one day before infection. The initial acute infection study, reported elsewhere, demonstrated a decrease in plasma- and cell-associated viremia at two weeks post-infection (PI) in FZD-treated cats as compared to placebo-treated cats. We hypothesized that this early alteration in plasma- and cell-associated viremia would alter the virus set point and ultimately affect the outcome of chronic infection. Here we provide data at one, two and three years PI for plasma- and/or cell-associated viremia, total lymphocyte counts and CD4:CD8 ratios. There was no difference in viremia or cell counts between treated and nontreated groups at all time points tested. Contrary to our hypothesis, these results suggest that treatment with a single agent anti-retroviral drug during acute lentivirus infection does not significantly alter viral load and immune function during the chronic, asymptomatic stage of infection.}, number={6}, journal={Viruses}, publisher={MDPI AG}, author={Miller, Michelle M. and Fogle, Jonathan E.}, year={2012}, month={Jun}, pages={954–962} }
 @article{fogle_tompkins_campbell_sumner_tompkins_2011, title={Fozivudine Tidoxil as Single-Agent Therapy Decreases Plasma and Cell-Associated Viremia during Acute Feline Immunodeficiency Virus Infection}, volume={25}, ISSN={["1939-1676"]}, DOI={10.1111/j.1939-1676.2011.0699.x}, abstractNote={Background:  Feline immunodeficiency virus (FIV) is a lentivirus that infects domestic and wild felidae and the course of disease is similar to that of human immunodeficiency virus infection. The thymidine nucleoside analog fozivudine (FZD) tidoxil is a lipid—zidovudine (ZDV) conjugate and member of the family of nucleoside reverse transcriptase (RT) inhibitors (NRTIs).}, number={3}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Fogle, J. E. and Tompkins, W. A. and Campbell, B. and Sumner, D. and Tompkins, M. B.}, year={2011}, pages={413–418} }
 @article{fogle_mexas_tompkins_tompkins_2010, title={CD4(+)CD25(+) T Regulatory Cells Inhibit CD8(+) IFN-gamma Production During Acute and Chronic FIV Infection Utilizing a Membrane TGF-beta-Dependent Mechanism}, volume={26}, ISSN={["1931-8405"]}, DOI={10.1089/aid.2009.0162}, abstractNote={CD8(+) lymphocytes are critical to the control and elimination of viral pathogens. Impaired CD8(+) responses are well recognized in lentiviral infections; however, the mechanisms underlying CD8(+) impairment remain elusive. Using the feline immunodeficiency virus (FIV) model for human AIDS, we reported previously that CD4(+)CD25(+) Treg cells in both the acute and long-term, asymptomatic phase of infection are constitutively activated and suppress CD4(+)CD25(-) T cell responses. In the current study, we have demonstrated that CD4(+)CD25(+) Treg cells suppress CD8(+) responses to immune stimulation during both the acute and chronic, asymptomatic phase of FIV infection and that the mechanism of suppression may be mediated by membrane-associated TGF-beta (mTGF-beta) on CD4(+)CD25(+) lymphocytes. Depletion of CD4(+)CD25(+) lymphocytes from lymph node suspensions significantly enhanced production of IFN-gamma during the acute phase of infection and coculture of CD8(+) lymphocytes with CD4(+)CD25(+) lymphocytes resulted in suppression of CD8(+) IFN-gamma during both the acute and chronic stages of infection. FACS analysis indicated that there was TGF-betaRII upregulation on CD8(+) cells from FIV(+) cats during the acute and chronic stage of infection. In addition, there was upregulation of mTGF-beta on the CD4(+)CD25(+) subset in chronically infected cats. In support of activation of the TGF-beta signaling pathway, Western blotting showed Smad 2 phosphorylation in CD8(+) targets following CD4(+)CD25(+)/CD8(+) coculture. These results demonstrate the suppressive effect CD4(+)CD25(+) Treg cells have on the CD8(+) immune response during the acute and chronic stages of FIV infection and suggest that the mechanism of suppression may be mediated by mTGF-beta.}, number={2}, journal={AIDS RESEARCH AND HUMAN RETROVIRUSES}, author={Fogle, Jonathan E. and Mexas, Angela M. and Tompkins, Wayne A. and Tompkins, Mary B.}, year={2010}, month={Feb}, pages={201–216} }
 @article{fogle_tompkins_tompkins_2010, title={CD4(+)CD25(+) T regulatory cells from FIV+ cats induce a unique anergic profile in CD8(+) lymphocyte targets}, volume={7}, ISSN={["1742-4690"]}, DOI={10.1186/1742-4690-7-97}, abstractNote={Abstract}, journal={RETROVIROLOGY}, author={Fogle, Jonathan E. and Tompkins, Wayne A. and Tompkins, Mary B.}, year={2010}, month={Nov} }
 @article{mexas_fogle_tompkins_tompkins_2008, title={CD4(+)CD25(+) regulatory T cells are infected and activated during acute FIV infection}, volume={126}, ISSN={["1873-2534"]}, DOI={10.1016/j.vetimm.2008.08.003}, abstractNote={HIV-induced AIDS may be mediated by the activation of immunosuppressive CD4+CD25+ T regulatory cells (Treg cells). Treg cells have been shown to regulate CD4+ and CD8+ immune responses to HIV and FIV antigens in vitro. We tested the hypothesis that Treg cells become infected and activated during the acute infection with FIV leading to the suppression of CD4+ T helper cell responses. Cats were experimentally infected with FIV-NCSU1 and blood and lymph node cells were collected at weekly intervals following inoculation. Real-time RT-PCR was used to determine plasma viremia and the relative expression of FIV, FoxP3, TGF-β, and GAPDH mRNA copies in CD4+CD25+ and CD4+CD25− T cell subsets. Flow cytometry was used to assess the absolute numbers of each cell type and the expression of surface TGF-β and intracellular FoxP3 in CD4+CD25+ and CD4+CD25− T cells at each time-point. Treg suppression of IL-2 production in CD4+ T helper cells was assessed by ELISPOT assays. Our results showed that peak viremia occurred at 2 weeks post infection and correlated with maximal infectivity in CD4+CD25+ T cell populations. FIV-gag-mRNA levels were higher in CD4+CD25+ T cells than CD4+CD25− T cells throughout the acute phase of infection. Induction of FoxP3 and TGF-β indicated activation of Treg cells during the acute stage infection, which was confirmed by Treg cell suppression of IL-2 production by CD4+ Th cells in an ELISPOT assay. Our findings support the hypothesis that early activation of Treg immunosuppressor function may limit an effective anti-FIV response, contributing to the establishment of chronic infection and the immunodeficiency caused by this virus.}, number={3-4}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Mexas, Angela M. and Fogle, Jonathan E. and Tompkins, Wayne A. and Tompkins, Mary B.}, year={2008}, month={Dec}, pages={263–272} }
 @inbook{tompkins_tompkins_mexas_fogle_2008, title={CD4+CD25+ Regulatory T Cells in Viral Infections}, ISBN={9780387779089 9780387779096}, url={http://dx.doi.org/10.1007/978-0-387-77909-6_22}, DOI={10.1007/978-0-387-77909-6_22}, booktitle={Regulatory T Cells and Clinical Application}, publisher={Springer US}, author={Tompkins, Wayne A. and Tompkins, Mary B. and Mexas, Angela M. and Fogle, Jonathan E.}, year={2008}, pages={407–422} }
 @article{smithberg_fogle_mexas_reckling_lankford_tompkins_dean_2008, title={In vivo depletion of CD4(+)CD25(+) regulatory T cells in cats}, volume={329}, ISSN={["0022-1759"]}, DOI={10.1016/j.jim.2007.09.015}, abstractNote={To establish a characterized model of regulatory T cell (Treg) depletion in the cat we assessed the kinetics of depletion and rebound in peripheral and central lymphoid compartments after treatment with anti-CD25 antibody as determined by cell surface markers and FOXP3 mRNA expression. An 82% decrease in circulating CD4+CD25+ Tregs was observed by day 11 after treatment. CD4+CD25+ cells were also reduced in the thymus (69%), secondary lymphoid tissues (66%), and gut (67%). Although CD4+CD25+ cells rebound by day 35 post-treatment, FOXP3 levels remain depressed suggesting anti-CD25 antibody treatment has a sustainable diminutive effect on the Treg population. To determine whether CD25+ Treg depletion strategies also deplete activated CD25+ effector cells, cats were immunized with feline immunodeficiency virus (FIV) p24-GST recombinant protein, allowing them to develop a measurable memory response, prior to depletion with anti-CD25 antibody. Anti-FIV p24-GST effector cell activity in peripheral blood after depletion was sustained as determined by antigen-specific T cell proliferation and humoral responses against FIV p24-GST with an ELISA for antigen-specific feline IgG. Furthermore, development of an anti-mouse response in Treg-depleted cats was similar to control levels indicating the retained capacity to respond to a novel antigen. We conclude that despite alterations in CD25+ cell levels during depletion, the feline immune system remains functional. We demonstrate here a model for the study of disease pathogenesis in the context of reduced numbers of immunosuppressive CD4+CD25+ Tregs throughout the feline immune system.}, number={1-2}, journal={JOURNAL OF IMMUNOLOGICAL METHODS}, author={Smithberg, S. Rochelle and Fogle, Jonathan E. and Mexas, Angela M. and Reckling, Stacie K. and Lankford, Susan M. and Tompkins, Mary B. and Dean, Gregg A.}, year={2008}, month={Jan}, pages={81–91} }
 @article{fogle_bissett_2007, title={Mucosal immunity and chronic idiopathic enteropathies in dogs}, volume={29}, number={5}, journal={Compendium on Continuing Education for the Practicing Veterinarian}, author={Fogle, J. E. and Bissett, S. A.}, year={2007}, pages={290–302} }
 @article{fogle_bissett_2005, title={Cholangiohepatitis in Cats}, volume={7}, number={4}, journal={Standards of Care- Emergency and Critical Care Medicine}, author={Fogle, JE and Bissett, SA}, year={2005}, month={May} }
 @article{fogle_2004, title={Pit Viper Envenomation in Dogs}, volume={6}, number={8}, journal={Standards of Care- Emergency and Critical Care Medicine}, author={Fogle, JE}, year={2004}, month={Sep} }