@article{lane_fu_sherry_tarbet_hurst_riabova_kazakova_egorova_clarke_leser_et al._2023, title={Efficacy of an isoxazole-3-carboxamide analog of pleconaril in mouse models of Enterovirus-D68 and Coxsackie B5}, volume={216}, ISSN={["1872-9096"]}, DOI={10.1016/j.antiviral.2023.105654}, abstractNote={Enteroviruses (EV) cause a number of life-threatening infectious diseases. EV-D68 is known to cause respiratory illness in children that can lead to acute flaccid myelitis. Coxsackievirus B5 (CVB5) is commonly associated with hand-foot-mouth disease. There is no antiviral treatment available for either. We have developed an isoxazole-3-carboxamide analog of pleconaril (11526092) which displayed potent inhibition of EV-D68 (IC50 58 nM) as well as other enteroviruses including the pleconaril-resistant Coxsackievirus B3-Woodruff (IC50 6-20 nM) and CVB5 (EC50 1 nM). Cryo-electron microscopy structures of EV-D68 in complex with 11526092 and pleconaril demonstrate destabilization of the EV-D68 MO strain VP1 loop, and a strain-dependent effect. A mouse respiratory model of EV-D68 infection, showed 3-log decreased viremia, favorable cytokine response, as well as statistically significant 1-log reduction in lung titer reduction at day 5 after treatment with 11526092. An acute flaccid myelitis neurological infection model did not show efficacy. 11526092 was tested in a mouse model of CVB5 infection and showed a 4-log TCID50 reduction in the pancreas. In summary, 11526092 represents a potent in vitro inhibitor of EV with in vivo efficacy in EV-D68 and CVB5 animal models suggesting it is worthy of further evaluation as a potential broad-spectrum antiviral therapeutic against EV.}, journal={ANTIVIRAL RESEARCH}, author={Lane, Thomas R. and Fu, Jianing and Sherry, Barbara and Tarbet, Bart and Hurst, Brett L. and Riabova, Olga and Kazakova, Elena and Egorova, Anna and Clarke, Penny and Leser, J. Smith and et al.}, year={2023}, month={Aug} }
 @article{lavigne_russell_sherry_ke_2021, title={Autocrine and paracrine interferon signalling as 'ring vaccination' and 'contact tracing' strategies to suppress virus infection in a host}, volume={288}, ISSN={["1471-2954"]}, DOI={10.1098/rspb.2020.3002}, abstractNote={The innate immune response, particularly the interferon response, represents a first line of defence against viral infections. The interferon molecules produced from infected cells act through autocrine and paracrine signalling to turn host cells into an antiviral state. Although the molecular mechanisms of IFN signalling have been well characterized, how the interferon response collectively contribute to the regulation of host cells to stop or suppress viral infection during early infection remain unclear. Here, we use mathematical models to delineate the roles of the autocrine and the paracrine signalling, and show that their impacts on viral spread are dependent on how infection proceeds. In particular, we found that when infection is well-mixed, the paracrine signalling is not as effective; by contrast, when infection spreads in a spatial manner, a likely scenario during initial infection in tissue, the paracrine signalling can impede the spread of infection by decreasing the number of susceptible cells close to the site of infection. Furthermore, we argue that the interferon response can be seen as a parallel to population-level epidemic prevention strategies such as ‘contact tracing’ or ‘ring vaccination’. Thus, our results here may have implications for the outbreak control at the population scale more broadly.}, number={1945}, journal={PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES}, author={Lavigne, G. Michael and Russell, Hayley and Sherry, Barbara and Ke, Ruian}, year={2021}, month={Feb} }
 @article{ferguson_foster_sherry_magness_nielsen_gookin_2019, title={Interferon-λ3 Promotes Epithelial Defense and Barrier Function Against Cryptosporidium parvum Infection}, volume={8}, ISSN={2352-345X}, url={http://dx.doi.org/10.1016/j.jcmgh.2019.02.007}, DOI={10.1016/j.jcmgh.2019.02.007}, abstractNote={Background & AimsThe epithelial response is critical for intestinal defense against Cryptosporidium, but is poorly understood. To uncover the host strategy for defense against Cryptosporidium, we examined the transcriptional response of intestinal epithelial cells (IECs) to C parvum in experimentally infected piglets by microarray. Up-regulated genes were dominated by targets of interferon (IFN) and IFN-λ3 was up-regulated significantly in infected piglet mucosa. Although IFN-λ has been described as a mediator of epithelial defense against viral pathogens, there is limited knowledge of any role against nonviral pathogens. Accordingly, the aim of the study was to determine the significance of IFN-λ3 to epithelial defense and barrier function during C parvum infection.MethodsThe significance of C parvum–induced IFN-λ3 expression was determined using an immunoneutralization approach in neonatal C57BL/6 mice. The ability of the intestinal epithelium to up-regulate IFN-λ2/3 expression in response to C parvum infection and the influence of IFN-λ2/3 on epithelial defense against C parvum invasion, intracellular development, and loss of barrier function was examined using polarized monolayers of a nontransformed porcine-derived small intestinal epithelial cell line (IPEC-J2). Specifically, changes in barrier function were quantified by measurement of transepithelial electrical resistance and transepithelial flux studies.ResultsImmunoneutralization of IFN-λ2/3 in C parvum–infected neonatal mice resulted in a significantly increased parasite burden, fecal shedding, and villus blunting with crypt hyperplasia during peak infection. In vitro, C parvum was sufficient to induce autonomous IFN-λ3 and interferon-stimulated gene 15 expression by IECs. Priming of IECs with recombinant human IFN-λ3 promoted cellular defense against C parvum infection and abrogated C parvum–induced loss of barrier function by decreasing paracellular permeability to sodium.ConclusionsThese studies identify IFN-λ3 as a key epithelial defense mechanism against C parvum infection. The epithelial response is critical for intestinal defense against Cryptosporidium, but is poorly understood. To uncover the host strategy for defense against Cryptosporidium, we examined the transcriptional response of intestinal epithelial cells (IECs) to C parvum in experimentally infected piglets by microarray. Up-regulated genes were dominated by targets of interferon (IFN) and IFN-λ3 was up-regulated significantly in infected piglet mucosa. Although IFN-λ has been described as a mediator of epithelial defense against viral pathogens, there is limited knowledge of any role against nonviral pathogens. Accordingly, the aim of the study was to determine the significance of IFN-λ3 to epithelial defense and barrier function during C parvum infection. The significance of C parvum–induced IFN-λ3 expression was determined using an immunoneutralization approach in neonatal C57BL/6 mice. The ability of the intestinal epithelium to up-regulate IFN-λ2/3 expression in response to C parvum infection and the influence of IFN-λ2/3 on epithelial defense against C parvum invasion, intracellular development, and loss of barrier function was examined using polarized monolayers of a nontransformed porcine-derived small intestinal epithelial cell line (IPEC-J2). Specifically, changes in barrier function were quantified by measurement of transepithelial electrical resistance and transepithelial flux studies. Immunoneutralization of IFN-λ2/3 in C parvum–infected neonatal mice resulted in a significantly increased parasite burden, fecal shedding, and villus blunting with crypt hyperplasia during peak infection. In vitro, C parvum was sufficient to induce autonomous IFN-λ3 and interferon-stimulated gene 15 expression by IECs. Priming of IECs with recombinant human IFN-λ3 promoted cellular defense against C parvum infection and abrogated C parvum–induced loss of barrier function by decreasing paracellular permeability to sodium. These studies identify IFN-λ3 as a key epithelial defense mechanism against C parvum infection.}, number={1}, journal={Cellular and Molecular Gastroenterology and Hepatology}, publisher={Elsevier BV}, author={Ferguson, Sylvia H. and Foster, Derek M. and Sherry, Barbara and Magness, Scott T. and Nielsen, Dahlia M. and Gookin, Jody L.}, year={2019}, pages={1–20} }
 @article{rivera-serrano_fritch_scholl_sherry_2017, title={A Cytoplasmic RNA Virus Alters the Function of the Cell Splicing Protein SRSF2}, volume={91}, ISSN={["1098-5514"]}, DOI={10.1128/jvi.02488-16}, abstractNote={ABSTRACT To replicate efficiently, viruses must create favorable cell conditions and overcome cell antiviral responses. We previously reported that the reovirus protein μ2 from strain T1L, but not strain T3D, represses one antiviral response: alpha/beta interferon signaling. We report here that T1L, but not T3D, μ2 localizes to nuclear speckles, where it forms a complex with the mRNA splicing factor SRSF2 and alters its subnuclear localization. Reovirus replicates in cytoplasmic viral factories, and there is no evidence that reovirus genomic or messenger RNAs are spliced, suggesting that T1L μ2 might target splicing of cell RNAs. Indeed, RNA sequencing revealed that reovirus T1L, but not T3D, infection alters the splicing of transcripts for host genes involved in mRNA posttranscriptional modifications. Moreover, depletion of SRSF2 enhanced reovirus replication and cytopathic effect, suggesting that T1L μ2 modulation of splicing benefits the virus. This provides the first report of viral antagonism of the splicing factor SRSF2 and identifies the viral protein that determines strain-specific differences in cell RNA splicing. IMPORTANCE Efficient viral replication requires that the virus create favorable cell conditions. Many viruses accomplish this by repressing specific antiviral responses. We demonstrate here that some mammalian reoviruses, RNA viruses that replicate strictly in the cytoplasm, express a protein variant that localizes to nuclear speckles, where it targets a cell mRNA splicing factor. Infection with a reovirus strain that targets this splicing factor alters splicing of cell mRNAs involved in the maturation of many other cell mRNAs. Depletion of this cell splicing factor enhances reovirus replication and cytopathic effect. Our results provide the first evidence of viral antagonism of this splicing factor and suggest that downstream consequences to the cell are global and benefit the virus.}, number={7}, journal={JOURNAL OF VIROLOGY}, author={Rivera-Serrano, Efrain E. and Fritch, Ethan J. and Scholl, Elizabeth H. and Sherry, Barbara}, year={2017}, month={Apr} }
 @article{rivera-serrano_sherry_2017, title={NF-kappa B activation is cell type-specific in the heart}, volume={502}, ISSN={["0042-6822"]}, DOI={10.1016/j.virol.2016.12.022}, abstractNote={Viral myocarditis is common and can progress to cardiac failure. Cardiac cell pro-inflammatory responses are critical for viral clearance, however sustained inflammatory responses contribute to cardiac damage. The transcription factor NF-κB regulates expression of many pro-inflammatory cytokines, but basal and induced activation of NF-κB in different cardiac cell types have not been compared. Here, we used primary cultures of cardiac myocytes and cardiac fibroblasts to identify cardiac cell type-specific events. We show that while viral infection readily stimulates activation of NF-κB in cardiac fibroblasts, cardiac myocytes are largely recalcitrant to activation of NF-κB. Moreover, we show that cardiac myocyte subpopulations differ in their NF-κB subcellular localization and identify the cis-Golgi as a cardiac myocyte-specific host compartment. Together, results indicate that NF-κB-dependent signaling in the heart is cardiac cell type-specific, likely reflecting mechanisms that have evolved to balance responses that can be either protective or damaging to the heart.}, journal={VIROLOGY}, author={Rivera-Serrano, Efrain E. and Sherry, Barbara}, year={2017}, month={Feb}, pages={133–143} }
 @article{rivera-serrano_deangelis_sherry_2017, title={Spontaneous activation of a MAVS-dependent antiviral signaling pathway determines high basal interferon-beta expression in cardiac myocytes}, volume={111}, DOI={10.1016/j.yjmcc.2017.08.008}, abstractNote={Viral myocarditis is a leading cause of sudden death in young adults as the limited turnover of cardiac myocytes renders the heart particularly vulnerable to viral damage. Viruses induce an antiviral type I interferon (IFN-α/β) response in essentially all cell types, providing an immediate innate protection. Cardiac myocytes express high basal levels of IFN-β to help pre-arm them against viral infections, however the mechanism underlying this expression remains unclear. Using primary cultures of murine cardiac and skeletal muscle cells, we demonstrate here that the mitochondrial antiviral signaling (MAVS) pathway is spontaneously activated in unstimulated cardiac myocytes but not cardiac fibroblasts or skeletal muscle cells. Results suggest that MAVS association with the mitochondrial-associated ER membranes (MAM) is a determinant of high basal IFN-β expression, and demonstrate that MAVS is essential for spontaneous high basal expression of IFN-β in cardiac myocytes and the heart. Together, results provide the first mechanism for spontaneous high expression of the antiviral cytokine IFN-β in a poorly replenished and essential cell type.}, journal={Journal of Molecular and Cellular Cardiology}, author={Rivera-Serrano, E. E. and DeAngelis, N. and Sherry, B.}, year={2017}, pages={102–113} }
 @article{friedenberg_chdid_keene_sherry_motsinger-reif_meurs_2016, title={Use of RNA-seq to identify cardiac genes and gene pathways differentially expressed between dogs with and without dilated cardiomyopathy}, volume={77}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.77.7.693}, abstractNote={OBJECTIVE To identify cardiac tissue genes and gene pathways differentially expressed between dogs with and without dilated cardiomyopathy (DCM). ANIMALS 8 dogs with and 5 dogs without DCM. PROCEDURES Following euthanasia, samples of left ventricular myocardium were collected from each dog. Total RNA was extracted from tissue samples, and RNA sequencing was performed on each sample. Samples from dogs with and without DCM were grouped to identify genes that were differentially regulated between the 2 populations. Overrepresentation analysis was performed on upregulated and downregulated gene sets to identify altered molecular pathways in dogs with DCM. RESULTS Genes involved in cellular energy metabolism, especially metabolism of carbohydrates and fats, were significantly downregulated in dogs with DCM. Expression of cardiac structural proteins was also altered in affected dogs. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that RNA sequencing may provide important insights into the pathogenesis of DCM in dogs and highlight pathways that should be explored to identify causative mutations and develop novel therapeutic interventions.}, number={7}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Friedenberg, Steven G. and Chdid, Lhoucine and Keene, Bruce and Sherry, Barbara and Motsinger-Reif, Alison and Meurs, Kathryn M.}, year={2016}, month={Jul}, pages={693–699} }
 @article{sherry_2015, title={Generating primary cultures of murine cardiac myocytes and cardiac fibroblasts to study viral myocarditis}, volume={1299}, journal={Cardiomyocytes: methods and protocols}, author={Sherry, B.}, year={2015}, pages={1–16} }
 @article{bogerd_skalsky_kennedy_furuse_whisnant_flores_schultz_putnam_barrows_sherry_et al._2014, title={Replication of Many Human Viruses Is Refractory to Inhibition by Endogenous Cellular MicroRNAs}, volume={88}, ISSN={["1098-5514"]}, DOI={10.1128/jvi.00985-14}, abstractNote={ABSTRACT The issue of whether viruses are subject to restriction by endogenous microRNAs (miRNAs) and/or by virus-induced small interfering RNAs (siRNAs) in infected human somatic cells has been controversial. Here, we address this question in two ways. First, using deep sequencing, we demonstrate that infection of human cells by the RNA virus dengue virus (DENV) or West Nile virus (WNV) does not result in the production of any virus-derived siRNAs or viral miRNAs. Second, to more globally assess the potential of small regulatory RNAs to inhibit virus replication, we used gene editing to derive human cell lines that lack a functional Dicer enzyme and that therefore are unable to produce miRNAs or siRNAs. Infection of these cells with a wide range of viruses, including DENV, WNV, yellow fever virus, Sindbis virus, Venezuelan equine encephalitis virus, measles virus, influenza A virus, reovirus, vesicular stomatitis virus, human immunodeficiency virus type 1, or herpes simplex virus 1 (HSV-1), failed to reveal any enhancement in the replication of any of these viruses, although HSV-1, which encodes at least eight Dicer-dependent viral miRNAs, did replicate somewhat more slowly in the absence of Dicer. We conclude that most, and perhaps all, human viruses have evolved to be resistant to inhibition by endogenous human miRNAs during productive replication and that dependence on a cellular miRNA, as seen with hepatitis C virus, is rare. How viruses have evolved to avoid inhibition by endogenous cellular miRNAs, which are generally highly conserved during metazoan evolution, remains to be determined. IMPORTANCE Eukaryotic cells express a wide range of small regulatory RNAs, including miRNAs, that have the potential to inhibit the expression of mRNAs that show sequence complementarity. Indeed, previous work has suggested that endogenous miRNAs have the potential to inhibit viral gene expression and replication. Here, we demonstrate that the replication of a wide range of pathogenic viruses is not enhanced in human cells engineered to be unable to produce miRNAs, indicating that viruses have evolved to be resistant to inhibition by miRNAs. This result is important, as it implies that manipulation of miRNA levels is not likely to prove useful in inhibiting virus replication. It also focuses attention on the question of how viruses have evolved to resist inhibition by miRNAs and whether virus mutants that have lost this resistance might prove useful, for example, in the development of attenuated virus vaccines.}, number={14}, journal={JOURNAL OF VIROLOGY}, author={Bogerd, Hal P. and Skalsky, Rebecca L. and Kennedy, Edward M. and Furuse, Yuki and Whisnant, Adam W. and Flores, Omar and Schultz, Kimberly L. W. and Putnam, Nicole and Barrows, Nicholas J. and Sherry, Barbara and et al.}, year={2014}, month={Jul}, pages={8065–8076} }
 @article{stebbing_irvin_rivera-serrano_boehme_ikizler_yoder_dermody_sherry_lyles_2013, title={An ITAM in a Nonenveloped Virus Regulates Activation of NF- B, Induction of Beta Interferon, and Viral Spread}, volume={88}, ISSN={0022-538X}, url={http://dx.doi.org/10.1128/JVI.02573-13}, DOI={10.1128/jvi.02573-13}, abstractNote={ABSTRACT Immunoreceptor tyrosine-based activation motifs (ITAMs) are signaling domains located within the cytoplasmic tails of many transmembrane receptors and associated adaptor proteins that mediate immune cell activation. ITAMs also have been identified in the cytoplasmic tails of some enveloped virus glycoproteins. Here, we identified ITAM sequences in three mammalian reovirus proteins: μ2, σ2, and λ2. We demonstrate for the first time that μ2 is phosphorylated, contains a functional ITAM, and activates NF-κB. Specifically, μ2 and μNS recruit the ITAM-signaling intermediate Syk to cytoplasmic viral factories and this recruitment requires the μ2 ITAM. Moreover, both the μ2 ITAM and Syk are required for maximal μ2 activation of NF-κB. A mutant virus lacking the μ2 ITAM activates NF-κB less efficiently and induces lower levels of the downstream antiviral cytokine beta interferon (IFN-β) than does wild-type virus despite similar replication. Notably, the consequences of these μ2 ITAM effects are cell type specific. In fibroblasts where NF-κB is required for reovirus-induced apoptosis, the μ2 ITAM is advantageous for viral spread and enhances viral fitness. Conversely, in cardiac myocytes where the IFN response is critical for antiviral protection and NF-κB is not required for apoptosis, the μ2 ITAM stimulates cellular defense mechanisms and diminishes viral fitness. Together, these results suggest that the cell type-specific effect of the μ2 ITAM on viral spread reflects the cell type-specific effects of NF-κB and IFN-β. This first demonstration of a functional ITAM in a nonenveloped virus presents a new mechanism for viral ITAM-mediated signaling with likely organ-specific consequences in the host.}, number={5}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Stebbing, R. E. and Irvin, S. C. and Rivera-Serrano, E. E. and Boehme, K. W. and Ikizler, M. and Yoder, J. A. and Dermody, T. S. and Sherry, B. and Lyles, D. S.}, year={2013}, month={Dec}, pages={2572–2583} }
 @article{irvin_zurney_ooms_chappell_dermody_sherry_2012, title={A Single-Amino-Acid Polymorphism in Reovirus Protein mu 2 Determines Repression of Interferon Signaling and Modulates Myocarditis}, volume={86}, ISSN={["0022-538X"]}, DOI={10.1128/jvi.06236-11}, abstractNote={ABSTRACT Myocarditis is indicated as the second leading cause of sudden death in young adults. Reovirus induces myocarditis in neonatal mice, providing a tractable model system for investigation of this important disease. Alpha/beta-interferon (IFN-α/β) treatment improves cardiac function and inhibits viral replication in patients with chronic myocarditis, and the host IFN-α/β response is a determinant of reovirus strain-specific differences in induction of myocarditis. Virus-induced IFN-β stimulates a signaling cascade that establishes an antiviral state and further induces IFN-α/β through an amplification loop. Reovirus strain-specific differences in induction of and sensitivity to IFN-α/β are associated with the viral M1, L2, and S2 genes. The reovirus M1 gene-encoded μ2 protein is a strain-specific repressor of IFN-β signaling, providing one possible mechanism for the variation in resistance to IFN and induction of myocarditis between different reovirus strains. We report here that μ2 amino acid 208 determines repression of IFN-β signaling and modulates reovirus induction of IFN-β in cardiac myocytes. Moreover, μ2 amino acid 208 determines reovirus replication, both in initially infected cardiac myocytes and after viral spread, by regulating the IFN-β response. Amino acid 208 of μ2 also influences the cytopathic effect in cardiac myocytes after spread. Finally, μ2 amino acid 208 modulates myocarditis in neonatal mice. Thus, repression of IFN-β signaling mediated by reovirus μ2 amino acid 208 is a determinant of the IFN-β response, viral replication and damage in cardiac myocytes, and myocarditis. These results demonstrate that a single amino acid difference between viruses can dictate virus strain-specific differences in suppression of the host IFN-β response and, consequently, damage to the heart.}, number={4}, journal={JOURNAL OF VIROLOGY}, author={Irvin, Susan C. and Zurney, Jennifer and Ooms, Laura S. and Chappell, James D. and Dermody, Terence S. and Sherry, Barbara}, year={2012}, month={Feb}, pages={2302–2311} }
 @article{li_sherry_2010, title={IFN-α expression and antiviral effects are subtype and cell type specific in the cardiac response to viral infection}, volume={396}, ISSN={0042-6822}, url={http://dx.doi.org/10.1016/j.virol.2009.10.013}, DOI={10.1016/j.virol.2009.10.013}, abstractNote={The interferon-β (IFN-β) response is critical for protection against viral myocarditis in several mouse models, and IFN-α or -β treatment is beneficial against human viral myocarditis. The IFN-β response in cardiac myocytes and cardiac fibroblasts forms an integrated network for organ protection; however, the different IFN-α subtypes have not been studied in cardiac cells. We developed a quantitative RT-PCR assay that distinguishes between 13 highly conserved IFN-α subtypes and found that reovirus T3D induces five IFN-α subtypes in primary cardiac myocyte and fibroblast cultures: IFN-α1, -α2, -α4, -α5, and -α8/6. Murine IFN-α1, -α2, -α4, or -α5 treatment induced IRF7 and ISG56 and inhibited reovirus T3D replication in both cell types. This first investigation of IFN-α subtypes in cardiac cells for any virus demonstrates that IFN-α is induced in cardiac cells, that it is both subtype and cell type specific, and that it is likely important in the antiviral cardiac response.}, number={1}, journal={Virology}, publisher={Elsevier BV}, author={Li, Lianna and Sherry, Barbara}, year={2010}, month={Jan}, pages={59–68} }
 @article{holm_pruijssers_li_danthi_sherry_dermody_2010, title={Interferon Regulatory Factor 3 Attenuates Reovirus Myocarditis and Contributes to Viral Clearance}, volume={84}, ISSN={["0022-538X"]}, DOI={10.1128/jvi.01742-09}, abstractNote={ABSTRACT Apoptosis is a pathological hallmark of encephalitis and myocarditis caused by reovirus in newborn mice. In cell culture models, the antiviral transcription factor interferon regulatory factor 3 (IRF-3) enhances reovirus-induced apoptosis following activation via retinoic acid inducible gene I and interferon promoter-stimulating factor 1. To determine the role of IRF-3 in reovirus disease, we infected newborn IRF-3+/+ and IRF-3−/− mice perorally with mildly virulent strain type 1 Lang (T1L) and fully virulent strain type 3 SA+ (T3SA+) and monitored infected animals for survival. Both wild-type and IRF-3−/− mice succumbed with equivalent frequencies to infection with T3SA+. However, the absence of IRF-3 was associated with significantly decreased survival rates following infection with T1L. The two virus strains achieved similar peak titers in IRF-3+/+ and IRF-3−/− mice in the intestine, brain, heart, liver, and spleen. However, by day 12 postinoculation, titers in all organs examined were 10- to 100-fold higher in IRF-3−/− mice than those in wild-type mice. Increased titers were associated with marked pathological changes in all organs examined, especially in the heart, where absence of IRF-3 resulted in severe myocarditis. Cellular and humoral immune responses were equivalent in wild-type and IRF-3−/− animals, suggesting that IRF-3 functions independently of the adaptive immune response to enhance reovirus clearance. Thus, IRF-3 serves to facilitate virus clearance and prevent tissue injury in response to reovirus infection.}, number={14}, journal={JOURNAL OF VIROLOGY}, author={Holm, Geoffrey H. and Pruijssers, Andrea J. and Li, Lianna and Danthi, Pranav and Sherry, Barbara and Dermody, Terence S.}, year={2010}, month={Jul}, pages={6900–6908} }
 @article{li_sevinsky_rowland_bundy_stephenson_sherry_2010, title={Proteomic Analysis Reveals Virus-Specific Hsp25 Modulation in Cardiac Myocytes}, volume={9}, ISSN={["1535-3907"]}, DOI={10.1021/pr901151k}, abstractNote={Viruses frequently infect the heart but clinical myocarditis is rare, suggesting that the cardiac antiviral response is uniquely effective. Indeed, the Type I interferon (IFN) response is cardiac cell-type specific and provides one integrated network of protection for the heart. Here, a proteomic approach was used to identify additional proteins that may be involved in the cardiac antiviral response. Reovirus-induced murine myocarditis reflects direct viral damage to cardiac cells and offers an excellent system for study. Primary cultures of murine cardiac myocytes were infected with myocarditic or nonmyocarditic reovirus strains, and whole cell lysates were compared by two-dimensional difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF/TOF) tandem mass spectrometry. Results were quantitative and reproducible and demonstrated that whole proteome changes clustered according to viral pathogenic phenotype. Moreover, the data suggest that the heat shock protein Hsp25 is modulated differentially by myocarditic and nonmyocarditic reoviruses and may play a role in the cardiac antiviral response. Members of seven virus families modulate Hsp25 or Hsp27 expression in a variety of cell types, suggesting that Hsp25 participation in the antiviral response may be widespread. However, results here provide the first evidence for a virus-induced decrease in Hsp25/27 and suggest that viruses may have evolved a mechanism to subvert this protective response, as they have for IFN.}, number={5}, journal={JOURNAL OF PROTEOME RESEARCH}, author={Li, Lianna and Sevinsky, Joel R. and Rowland, Megan D. and Bundy, Jonathan L. and Stephenson, James L. and Sherry, Barbara}, year={2010}, month={May}, pages={2460–2471} }
 @article{zurney_kobayashi_holm_dermody_sherry_2009, title={Reovirus mu 2 Protein Inhibits Interferon Signaling through a Novel Mechanism Involving Nuclear Accumulation of Interferon Regulatory Factor 9}, volume={83}, ISSN={["1098-5514"]}, DOI={10.1128/JVI.01787-08}, abstractNote={ABSTRACT The secreted cytokine alpha/beta interferon (IFN-α/β) binds its receptor to activate the Jak-STAT signal transduction pathway, leading to formation of the heterotrimeric IFN-stimulated gene factor 3 (ISGF3) transcription complex for induction of IFN-stimulated genes (ISGs) and establishment of an antiviral state. Many viruses have evolved countermeasures to inhibit the IFN pathway, thereby subverting the innate antiviral response. Here, we demonstrate that the mildly myocarditic reovirus type 1 Lang (T1L), but not the nonmyocarditic reovirus type 3 Dearing, represses IFN induction of a subset of ISGs and that this repressor function segregates with the T1L M1 gene. Concordantly, the T1L M1 gene product, μ2, dramatically inhibits IFN-β-induced reporter gene expression. Surprisingly, T1L infection does not degrade components of the ISGF3 complex or interfere with STAT1 or STAT2 nuclear translocation as has been observed for other viruses. Instead, infection with T1L or reassortant or recombinant viruses containing the T1L M1 gene results in accumulation of interferon regulatory factor 9 (IRF9) in the nucleus. This effect has not been previously described for any virus and suggests that μ2 modulates IRF9 interactions with STATs for both ISGF3 function and nuclear export. The M1 gene is a determinant of virus strain-specific differences in the IFN response, which are linked to virus strain-specific differences in induction of murine myocarditis. We find that virus-induced myocarditis is associated with repression of IFN function, providing new insights into the pathophysiology of this disease. Together, these data provide the first report of an increase in IRF9 nuclear accumulation associated with viral subversion of the IFN response and couple virus strain-specific differences in IFN antagonism to the pathogenesis of viral myocarditis.}, number={5}, journal={JOURNAL OF VIROLOGY}, author={Zurney, Jennifer and Kobayashi, Takeshi and Holm, Geoffrey H. and Dermody, Terence S. and Sherry, Barbara}, year={2009}, month={Mar}, pages={2178–2187} }
 @misc{sherry_2009, title={Rotavirus and Reovirus Modulation of the Interferon Response}, volume={29}, ISSN={["1557-7465"]}, DOI={10.1089/jir.2009.0072}, abstractNote={The mammalian reoviruses and rotaviruses have evolved specific mechanisms to evade the Type I interferon (IFN) antiviral response. Rotavirus likely represses the IFN response by at least 4 mechanisms. First, the rotavirus protein NSP1, most likely functioning as an E3 ligase, can induce proteasome-dependent degradation of the transcription factors IRF3, IRF5, and IRF7 to prevent their induction of IFN. Second, NSP1 can induce proteasome-dependent degradation of the ubiquitin ligase complex protein beta-TrCP, resulting in stabilization of I kappaB and concomitant failure of virus to activate NF-kappaB for induction of IFN. Third, rotavirus may sequester NF-kappaB in viroplasms. And fourth, rotavirus can prevent STAT1 and STAT2 nuclear translocation. The predominant mechanism for rotavirus inhibition of the IFN response is likely both rotavirus strain-specific and cell type-specific. The mammalian reoviruses also display strain-specific differences in their modulation of the IFN response. Reovirus activates RIG-I and IPS-1 for phosphorylation of IRF3. Reovirus-induced activation of MDA5 also participates in induction if IFN-beta, perhaps through activation of NF-kappaB. Reovirus likely inhibits the IFN response by at least 3 virus strain-specific mechanisms. First, the reovirus mu2 protein can induce an unusual nuclear accumulation of IRF9 and repress IFN-stimulated gene (ISG) expression, most likely by disrupting IRF9 function as part of the heterotrimeric transcription factor complex, ISGF3. Second, the reovirus sigma 3 protein can bind dsRNA and prevent activation of the latent antiviral effector protein PKR. And third, genetic approaches have identified the reovirus lambda 2 and sigma 2 proteins in virus strain-specific modulation of the IFN response, but the significance remains unclear. In sum, members of the family Reoviridae have evolved a variety of mechanisms to subvert the host's innate protective response.}, number={9}, journal={JOURNAL OF INTERFERON AND CYTOKINE RESEARCH}, author={Sherry, Barbara}, year={2009}, month={Sep}, pages={559–567} }
 @article{sherry_zurney_kobayashi_holm_dermody_2008, title={237 Reovirus inhibits interferon signaling through a novel mechanism involving nuclear accumulation of IRF9}, volume={43}, ISSN={1043-4666}, url={http://dx.doi.org/10.1016/j.cyto.2008.07.302}, DOI={10.1016/j.cyto.2008.07.302}, number={3}, journal={Cytokine}, publisher={Elsevier BV}, author={Sherry, Barbara and Zurney, Jennifer and Kobayashi, Takeshi and Holm, Geoffrey H. and Dermody, Terence S.}, year={2008}, month={Sep}, pages={296} }
 @article{zurney_howard_sherry_2007, title={Basal expression levels of IFNAR and Jak-STAT components are determinants of cell-type-specific differences in cardiac antiviral responses}, volume={81}, ISSN={["0022-538X"]}, DOI={10.1128/JVI.01172-07}, abstractNote={ABSTRACT Viral myocarditis is an important human disease, and reovirus-induced murine myocarditis provides an excellent model system for study. Cardiac myocytes, like neurons in the central nervous system, are not replenished, yet there is no cardiac protective equivalent to the blood-brain barrier. Thus, cardiac myocytes may have evolved a unique antiviral response relative to readily replenished cell types, such as cardiac fibroblasts. Our previous comparisons of these two cell types revealed a conundrum: reovirus T3D induces more beta-interferon (IFN-β) mRNA in cardiac myocytes, yet there is a greater induction of IFN-stimulated genes (ISGs) in cardiac fibroblasts. Here, we investigated possible underlying molecular determinants. We found that greater basal expression of IFN-β in cardiac myocytes results in greater basal activated nuclear STAT1 and STAT2 and greater basal ISG mRNA expression and provides greater basal antiviral protection relative to cardiac fibroblasts. Conversely, cardiac fibroblasts express greater basal IFN-α/β receptor 1 (IFNAR1) and greater basal cytoplasmic Jak1, Tyk2, STAT2, and IRF9, leading to a greater increase in reovirus T3D- or IFN-induced nuclear activated STAT1 and STAT2 and greater induction of ISGs for a greater IFN-induced antiviral protection relative to cardiac myocytes. Our results suggest that high basal IFN-β expression in cardiac myocytes prearms this vulnerable, nonreplenishable cell type, while high basal expression of IFNAR1 and latent Jak-STAT components in adjacent cardiac fibroblasts renders these cells more responsive to IFN and prevents them from inadvertently serving as a reservoir for viral replication and spread to cardiac myocytes. These studies provide the first indication of an integrated network of cell-type-specific innate immune components for organ protection.}, number={24}, journal={JOURNAL OF VIROLOGY}, author={Zurney, Jennifer and Howard, Kristina E. and Sherry, Barbara}, year={2007}, month={Dec}, pages={13668–13680} }
 @article{holm_zurney_tumilasci_leveille_danthi_hiscott_sherry_dermody_2007, title={Retinoic acid-inducible gene-I and interferon-beta promoter stimulator-1 augment proapoptotic responses following mammalian reovirus infection via interferon regulatory factor-3}, volume={282}, ISSN={["1083-351X"]}, DOI={10.1074/jbc.M702112200}, abstractNote={During viral infection, cells initiate antiviral responses to contain replication and inhibit virus spread. One protective mechanism involves activation of transcription factors interferon regulatory factor-3 (IRF-3) and NF-κB, resulting in secretion of the antiviral cytokine, interferon-β. Another is induction of apoptosis, killing the host cell before virus disseminates. Mammalian reovirus induces both interferon-β and apoptosis, raising the possibility that both pathways are initiated by a common cellular sensor. We show here that reovirus activates IRF-3 with kinetics that parallel the activation of NF-κB, a known mediator of reovirus-induced apoptosis. Activation of IRF-3 requires functional retinoic acid inducible gene-I and interferon-β promoter stimulator-1, but these intracellular sensors are dispensable for activation of NF-κB. Interferon-β promoter stimulator-1 and IRF-3 are required for efficient apoptosis following reovirus infection, suggesting a common mechanism of antiviral cytokine induction and activation of the cell death response.}, number={30}, journal={JOURNAL OF BIOLOGICAL CHEMISTRY}, author={Holm, Geoffrey H. and Zurney, Jennifer and Tumilasci, Vanessa and Leveille, Simon and Danthi, Pranav and Hiscott, John and Sherry, Barbara and Dermody, Terence S.}, year={2007}, month={Jul}, pages={21953–21961} }
 @article{stewart_smoak_blum_sherry_2005, title={Basal and reovirus-induced beta interferon (IFN-beta) and IFN-beta-stimulated gene expression are cell type specific in the cardiac protective response}, volume={79}, ISSN={["1098-5514"]}, DOI={10.1128/JVI.79.5.2979-2987.2005}, abstractNote={ABSTRACT Viral myocarditis is an important human disease, with a wide variety of viruses implicated. Cardiac myocytes are not replenished yet are critical for host survival and thus may have a unique response to infection. Previously, we determined that the extent of reovirus induction of beta interferon (IFN-β) and IFN-β-mediated protection in primary cardiac myocyte cultures was inversely correlated with the extent of reovirus-induced cardiac damage in a mouse model. Surprisingly, and in contrast, the IFN-β response did not determine reovirus replication in skeletal muscle cells. Here we compared the IFN-β response in cardiac myocytes to that in primary cardiac fibroblast cultures, a readily replenished cardiac cell type. We compared basal and reovirus-induced expression of IFN-β, IRF-7 (an interferon-stimulated gene [ISG] that further induces IFN-β), and another ISG (561) in the two cell types by using real-time reverse transcription-PCR. Basal IFN-β, IRF-7, and 561 expression was higher in cardiac myocytes than in cardiac fibroblasts. Reovirus T3D induced greater expression of IFN-β in cardiac myocytes than in cardiac fibroblasts but equivalent expression of IRF-7 and 561 in the two cell types (though fold induction for IRF-7 and 561 was higher in fibroblasts than in myocytes because of the differences in basal expression). Interestingly, while reovirus replicated to equivalent titers in cardiac myocytes and cardiac fibroblasts, removal of IFN-β resulted in 10-fold-greater reovirus replication in the fibroblasts than in the myocytes. Together the data suggest that the IFN-β response controls reovirus replication equivalently in the two cell types. In the absence of reovirus-induced IFN-β, however, reovirus replicates to higher titers in cardiac fibroblasts than in cardiac myocytes, suggesting that the higher basal IFN-β and ISG expression in myocytes may play an important protective role.}, number={5}, journal={JOURNAL OF VIROLOGY}, author={Stewart, MJ and Smoak, K and Blum, MA and Sherry, B}, year={2005}, month={Mar}, pages={2979–2987} }
 @article{sherry_2005, title={Organ-specific roles for transcription factor NF-kappa B in reovirus-induced apoptosis and disease}, volume={115}, number={9}, journal={Journal of Clinical Investigation}, author={Sherry, B.}, year={2005}, pages={2341–2350} }
 @article{debiasi_robinson_sherry_bouchard_brown_rizeq_long_tyler_2004, title={Caspase inhibition protects against reovirus-induced myocardial injury in vitro and in vivo}, volume={78}, ISSN={["1098-5514"]}, DOI={10.1128/JVI.78.20.11040-11050.2004}, abstractNote={ABSTRACT Viral myocarditis is a disease with a high morbidity and mortality. The pathogenesis of this disease remains poorly characterized, with components of both direct virus-mediated and secondary inflammatory and immune responses contributing to disease. Apoptosis has increasingly been viewed as an important mechanism of myocardial injury in noninfectious models of cardiac disease, including ischemia and failure. Using a reovirus murine model of viral myocarditis, we characterized and targeted apoptosis as a key mechanism of virus-associated myocardial injury in vitro and in vivo. We demonstrated caspase-3 activation, in conjunction with terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling and annexin binding, in cardiac myocytes after myocarditic viral infection in vitro. We also demonstrated a tight temporal and geographical correlation between caspase-3 activation, histologic injury, and viral load in cardiac tissue after myocarditic viral infection in vivo. Two pharmacologic agents that broadly inhibit caspase activity, Q-VD-OPH and Z-VAD(OMe)-FMK, effectively inhibited virus-induced cellular death in vitro. The inhibition of caspase activity in vivo by the use of pharmacologic agents as well as genetic manipulation reduced virus-induced myocardial injury by 40 to 60% and dramatically improved survival in infected caspase-3-deficient animals. This study indicates that apoptosis plays a critical role in mediating cardiac injury in the setting of viral myocarditis and is the first demonstration that caspase inhibition may serve as a novel therapeutic strategy for this devastating disease.}, number={20}, journal={JOURNAL OF VIROLOGY}, author={DeBiasi, RL and Robinson, BA and Sherry, B and Bouchard, R and Brown, RD and Rizeq, M and Long, C and Tyler, KL}, year={2004}, month={Oct}, pages={11040–11050} }
 @article{stewart_blum_sherry_2003, title={PKR's protective role in viral myocarditis}, volume={314}, ISSN={["0042-6822"]}, DOI={10.1016/S0042-6822(03)00414-8}, abstractNote={Reovirus-induced murine myocarditis provides an excellent model for the human disease. Previously, we showed that reovirus induction of and sensitivity to interferon-beta (IFN-beta) are important determinants of protection against cardiac damage. IFN-beta induces a number of genes with antiviral activities, including the dsRNA-activated protein kinase, PKR. Once bound to viral dsRNA, PKR becomes activated and phosphorylates eukaryotic initiation factor-2 alpha (eIF2 alpha) leading to the cessation of host cell translation. Additionally, activated PKR can exert its antiviral effects by inducing phosphorylation of I kappa B, leading to the activation of the transcription factor NF kappa B and subsequent induction of IFN-beta. Thus, activated PKR can both induce and be induced by IFN-beta. Recently, numerous reports have shown PKR to be dispensable for both induction of IFN as well as protection against disease. However, both PKR's role in the heart in response to viral infection and its ability to prevent cardiac damage have gone largely unexplored. Here, we demonstrate PKR to be critical for viral induction of IFN-beta in primary cardiac myocyte cultures. Additionally, we show that loss of PKR leads to an increase in virulence for both myocarditic and nonmyocarditic reoviruses. Finally, we demonstrate PKR to be critical for protection against reovirus-induced viral myocarditis.}, number={1}, journal={VIROLOGY}, author={Stewart, MJ and Blum, MA and Sherry, B}, year={2003}, month={Sep}, pages={92–100} }
 @article{azzam-smoak_noah_stewart_blum_sherry_2002, title={Interferon regulatory factor-1, interferon-beta, and reovirus-induced myocarditis}, volume={298}, ISSN={["0042-6822"]}, DOI={10.1006/viro.2002.1470}, abstractNote={Viral myocarditis is an important human disease, and reovirus-induced myocarditis in mice provides an excellent model to study direct viral damage to the heart. Previously, we showed that reovirus induction of and sensitivity to interferon-beta (IFN-beta) is an important determinant of viral pathogenicity in the heart and that the transcription factor interferon regulatory factor-3 (IRF-3) is required for reovirus induction of IFN-beta in primary cardiac myocyte cultures. Given several lines of evidence suggesting a possible distinctive environment for IRFs in the heart, we have now focused on IRF-1. Previous studies demonstrated that viruses, double-stranded-RNA (dsRNA), and IFN-alpha/beta can each induce IRF-1 and that IRF-1 plays a role in dsRNA, but perhaps not viral, induction of IFN-alpha/beta. Importantly, none of these studies used a virus with a dsRNA genome (such as reovirus), none of them used a highly differentiated nonlymphoid cell type, and none of them addressed whether viral induction of IRF-1 is direct or is mediated through viral induction of IFN-beta. Indeed, as recently as this year it has been assumed that viral induction of IRF-1 is direct. Here, we found that reovirus induced IRF-1 in primary cardiac myocyte cultures, but that IRF-1 was not required for reovirus induction of IFN-beta. Surprisingly, we found that reovirus failed to induce IRF-1 in the absence of the IFN-alpha/beta response. This provides the first evidence that viruses may not induce IRF-1 directly. Finally, nonmyocarditic reovirus strains induced more cardiac lesions in mice deficient for IRF-1 than they did in wildtype mice, directly demonstrating a protective role for IRF-1. Together, the results indicate that while IRF-1 is downstream of the IFN-beta response, it plays an important protective role against viral myocarditis.}, number={1}, journal={VIROLOGY}, author={Azzam-Smoak, K and Noah, DL and Stewart, MJ and Blum, MA and Sherry, B}, year={2002}, month={Jun}, pages={20–29} }
 @article{heggen-peay_qureshi_edens_sherry_wakenell_ph o'connell_schat_2002, title={Isolation of a reovirus from poult enteritis and mortality syndrome and its pathogenicity in turkey poults}, volume={46}, ISSN={["0005-2086"]}, DOI={10.1637/0005-2086(2002)046[0032:IOARFP]2.0.CO;2}, abstractNote={SUMMARY. Poult enteritis and mortality syndrome (PEMS) is an acute, infectious intestinal disease of turkey poults, characterized by high mortality and 100% morbidity, that decimated the turkey industry in the mid-1990s. The etiology of PEMS is not completely understood. This report describes the testing of various filtrates of fecal material from control and PEMS-affected poults by oral inoculation into poults under experimental conditions, the subsequent isolation of a reovirus, ARV-CU98, from one of the PEMS fecal filtrates, and in vivo and in vitro studies conducted to determine the pathogenicity of ARV-CU98 in turkey poults. In order to identify a filtrate fraction of fecal material containing a putative etiologic agent, poults were challenged in two independent experiments with 220- and 100-nm filtrates of fecal material from PEMS-negative and PEMS-positive poults. The 100-nm filtrate was chosen for further evaluation because poults inoculated with this filtrate exhibited mortality and significantly lower (P ≤ 0.05) body weight and relative bursa weight, three clinical signs associated with PEMS. These results were confirmed in a third experiment with 100-nm fecal filtrates from a separate batch of PEMS fecal material. In Experiment 3, body weight and relative bursa and thymus weights were significantly lower (P ≤ 0.05) in poults inoculated with 100-nm filtrate of PEMS fecal material as compared with poults inoculated with 100-nm filtrate of control fecal material. Subsequently, a virus was isolated from the 100-nm PEMS fecal filtrate and propagated in liver cells. This virus was identified as a reovirus on the basis of cross-reaction with antisera against avian reovirus (FDO strain) as well as by electrophoretic analysis and was designated ARV-CU98. When inoculated orally into poults reared under controlled environmental conditions in isolators, ARV-CU98 was associated with a higher incidence of thymic hemorrhaging and gaseous intestines. In addition, relative bursa and liver weights were significantly lower (P ≤ 0.05) in virus-inoculated poults as compared with controls. Virus was successfully reisolated from virus-challenged poults but not from control birds. Furthermore, viral antigen was detected by immunofluorescence in liver sections from virus-challenged poults at 3 and 6 days postinfection and virus was isolated from liver at 6 days postinfection, suggesting that ARV-CU98 replicates in the liver. In addition to a decrease in liver weight, there was a functional degeneration as indicated by altered plasma alanine aminotransferase and aspartate aminotransferase activities in virus poults as compared with controls. Although this reovirus does not induce fulminating PEMS, our results demonstrated that ARV-CU98 does cause some of the clinical signs in PEMS, including intestinal alterations and significantly lower relative bursa and liver weights. ARV-CU98 may contribute directly to PEMS by affecting the intestine, bursa, and liver and may contribute indirectly by increasing susceptibility to opportunistic pathogens that facilitate development of clinical PEMS.}, number={1}, journal={AVIAN DISEASES}, author={Heggen-Peay, CL and Qureshi, MA and Edens, FW and Sherry, B and Wakenell, PS and PH O'Connell and Schat, KA}, year={2002}, pages={32–47} }
 @article{sherry_2002, title={The role of interferon regulatory factors in the cardiac response to viral infection}, volume={15}, ISSN={["1557-8976"]}, DOI={10.1089/088282402317340206}, abstractNote={Reovirus-induced murine myocarditis provides an excellent model for the human disease. Cardiac tissue damage varies between reovirus strains, and is caused by a direct viral cytopathogenic effect. One determinant of virus-induced cardiac tissue damage is the cardiac interferon-beta (IFN-beta) response to viral infection. Nonmyocarditic reoviruses induce more IFN-beta and/or are more sensitive to the antiviral effects of IFN-beta in cardiac cells than myocarditis reoviruses. The roles of interferon regulatory factors (IRFs) in the cardiac response to viral infection are reviewed, and results suggest possible cardiac-specific variations in IRF-3 and IRF-1 function. In addition, data are presented indicating that the role of IRF-2 in regulation of IFN-beta expression is cell type-specific and differs between skeletal and cardiac muscle cells. Together, results suggest that the heart may provide a unique environment for IRF function, critical for protection against virus-induced cardiac damage.}, number={1}, journal={VIRAL IMMUNOLOGY}, author={Sherry, B}, year={2002}, pages={17–28} }
 @article{debiasi_edelstein_sherry_tyler_2001, title={Calpain inhibition protects against virus-induced apoptotic myocardial injury}, volume={75}, ISSN={["1098-5514"]}, DOI={10.1128/JVI.75.1.351-361.2001}, abstractNote={ABSTRACT Viral myocarditis is an important cause of human morbidity and mortality for which reliable and effective therapy is lacking. Using reovirus strain 8B infection of neonatal mice, a well-characterized experimental model of direct virus-induced myocarditis, we now demonstrate that myocardial injury results from apoptosis. Proteases play a critical role as effectors of apoptosis. The activity of the cysteine protease calpain increases in reovirus-infected myocardiocytes and can be inhibited by the dipeptide alpha-ketoamide calpain inhibitorZ-Leu-aminobutyric acid-CONH(CH2)3-morpholine (CX295). Treatment of reovirus-infected neonatal mice with CX295 protects them against reovirus myocarditis as documented by (i) a dramatic reduction in histopathologic evidence of myocardial injury, (ii) complete inhibition of apoptotic myocardial cell death as identified by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling, (iii) a reduction in serum creatine phosphokinase, and (iv) improved weight gain. These findings are the first evidence for the importance of a calpain-associated pathway of apoptotic cell death in viral disease. Inhibition of apoptotic signaling pathways may be an effective strategy for the treatment of viral disease in general and viral myocarditis in particular.}, number={1}, journal={JOURNAL OF VIROLOGY}, author={DeBiasi, RL and Edelstein, CL and Sherry, B and Tyler, KL}, year={2001}, month={Jan}, pages={351–361} }
 @article{noah_blum_sherry_1999, title={Interferon regulatory factor 3 is required for viral induction of beta interferon in primary cardiac myocyte cultures}, volume={73}, number={12}, journal={Journal of Virology}, author={Noah, D. L. and Blum, M. A. and Sherry, B.}, year={1999}, pages={10208–10213} }
 @inbook{sherry_1998, title={Pathogenesis of reovirus myocarditis}, volume={233}, DOI={10.1007/978-3-642-72095-6_3}, abstractNote={Acute myocarditis (Aretz et al. 1986) is prevalent in humans, with reports suggesting that 5%–20% of the population has suffered some form of viral myocarditis (Bandt et al. 1979; Okuni et al. 1975; Woodruff 1980). It is often fatal in infants (Cherry 1995; Kaplan et al. 1983; Martin et al. 1994). In older individuals the acute disease usually resolves but can progress to chronic myocarditis and/or dilated cardiomyopathy (Archard et al. 1991; Kandolph et al. 1991; Keeling et al. 1994; Martino et al. 1994; Matsumori and Kawai 1982; Morimoto et al. 1992; Olsen 1992; Sole and Liu 1994) with concomitant cardiac failure (Borggrefe et al. 1994; Di Lenarda et al. 1994). Enteroviruses (mainly coxsackieviruses) most likely account for 20%–50% or more of the cases (Archard et al. 1991; Bowles et al. 1986; Easton and Eglin 1988; Kandolph et al. 1987, 1991; Tracy et al. 1990a,b; Weiss et al. 1991), and there is compelling evidence that enterovirus chronic myocarditis and acute myocarditis are immune-mediated (Cook et al. 1995; Guthrie et al. 1984; Hashimoto et al. 1983; Huber 1992; Huber et al. 1988; Kishimoto and Abelmann 1990; Klingel et al. 1996; Leslie et al. 1989; Liu et al. 1995; Martino et al. 1995; Rose et al. 1988, 1992; Schwimmbeck et al. 1996; Wolfgram et al. 1985; Woodruff 1980).}, booktitle={Reoviruses. II, Cytopathogenicity and pathogenesis}, publisher={New York: Springer}, author={Sherry, B.}, editor={K. L. Tyler and Oldstone, M. B. A.Editors}, year={1998}, pages={51–66} }
 @article{sherry_torres_blum_1998, title={Reovirus induction of and sensitivity to beta interferon in cardiac myocyte cultures correlate with induction of myocarditis and are determined by viral core proteins}, volume={72}, number={2}, journal={Journal of Virology}, author={Sherry, B. and Torres, J. and Blum, M. A.}, year={1998}, pages={1314–1323} }
 @article{brentano_noah_brown_sherry_1998, title={The reovirus protein mu2, encoded by the M1 gene, is an RNA-binding protein}, volume={72}, number={10}, journal={Journal of Virology}, author={Brentano, L. and Noah, D. L. and Brown, E. G. and Sherry, B.}, year={1998}, pages={8354–8357} }
 @article{roner_nepliouev_sherry_joklik_1997, title={Construction and characterization of a reovirus double temperature-sensitive mutant}, volume={94}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.94.13.6826}, abstractNote={The infectious reovirus RNA system was used to construct a mutant with two temperature-sensitive (ts) lesions in genome segments M2 and S2, respectively. The double mutant is about 300 times more ts than either of its parents, which are about 1,500 and 170 times more ts than their wild-type parent reovirus ST3 strain Dearing. At 39 degrees C the double mutant is essentially unable to multiply. In spite of its striking temperature sensitivity, the double mutant elicits the formation of significant amounts of neutralizing antibodies in newborn mice. Possible mechanisms responsible for this are discussed, as is the significance of this double ts mutant in relation to current searches for safe and efficient vaccine strains.}, number={13}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Roner, MR and Nepliouev, I and Sherry, B and Joklik, WK}, year={1997}, month={Jun}, pages={6826–6830} }
 @article{weigler_guy_nasisse_hancock_sherry_1997, title={Effect of a live attenuated intranasal vaccine on latency and shedding of feline herpesvirus 1 in domestic cats}, volume={142}, ISSN={["0304-8608"]}, DOI={10.1007/s007050050250}, abstractNote={A prospective study was conducted that evaluated duration of virus shedding through acute and experimentally-induced recurrent disease episodes in 12 cats, and tissue distribution of latent infections, following intranasal vaccination with a temperature sensitive (ts) mutant strain of feline herpesvirus 1 (FHV1). Six of these cats were challenged with a virulent field strain of the agent to assess the extent to which vaccination affected subsequent shedding of virus and the establishment of latent infections. Virus isolation (VI) tests were done in parallel with a polymerase chain reaction (PCR) assay to compare the performance of each diagnostic method. The PCR confirmed that all 12 cats shed virus throughout the periods of vaccination, challenge or mock-challenge, and a cyclophosphamide-dexamethasone stress protocol to reactivate latent infections. Shedding to the tsFHV1 was documented by VI for up to 25 days following vaccination and for up to 15 days following challenge, but not after experimental stress. Overall, FHV1 was present in 144 of 300 (48%) cat-days of testing by PCR compared to 32 of 300 (11%) by VI. The frequency and distribution of latent FHV1 detected in neurologic, ophthalmic, and other tissues by PCR were identical for vaccine-only and vaccine-challenge groups, thereby disproving previous hypotheses that tsFHV1 mutants administered by this route protect against latency.}, number={12}, journal={ARCHIVES OF VIROLOGY}, author={Weigler, BJ and Guy, JS and Nasisse, MP and Hancock, SI and Sherry, B}, year={1997}, pages={2389–2400} }
 @article{weigler_babineau_sherry_nasisse_1997, title={High sensitivity polymerase chain reaction assay for active and latent feline herpesvirus-1 infections in domestic cats}, volume={140}, ISSN={["0042-4900"]}, DOI={10.1136/vr.140.13.335}, abstractNote={A polymerase chain reaction (PCR) assay was developed and used to detect feline herpesvirus-1 (FHV-1) in conjunctival and oropharyngeal swabs, and in latently infected tissues (trigeminal ganglia, optic nerves, optic chiasma, olfactory bulbs and corneas) collected from 10 experimentally infected cats. There was good agreement between parallel tests of the swab specimens by PCR and virus isolation assay during the phase of acute, latent and recurrent disease episodes (kappa=0.63, P<0.001). The PCR reliably detected ≤240 copies of FHV-1 template DNA, significantly improving upon previously published PCR assays for the agent.}, number={13}, journal={VETERINARY RECORD}, author={Weigler, BJ and Babineau, CA and Sherry, B and Nasisse, MP}, year={1997}, month={Mar}, pages={335–338} }
 @article{sherry_baty_blum_1996, title={Reovirus-induced acute myocarditis in mice correlates with viral RNA synthesis rather than generation of infectious virus in cardiac myocytes}, volume={70}, number={10}, journal={Journal of Virology}, author={Sherry, B. and Baty, C.J. and Blum, M.A.}, year={1996}, pages={6709–6715} }
 @article{mcgahan_harned_goralska_sherry_fleisher_1995, title={TRANSFERRIN SECRETION BY LENS EPITHELIAL-CELLS IN CULTURE}, volume={60}, ISSN={["0014-4835"]}, DOI={10.1016/S0014-4835(05)80008-9}, abstractNote={Transferrin (Tf), the plasma iron transport protein which supports cell proliferation and differentiation and has bacteriostatic, antioxidant and anti-inflammatory activity, has been found in relatively high concentrations in the intraocular fluids. Intraocular synthesis of Tf has recently been demonstrated, although the intraocular tissue(s) responsible have not been identified. We designed this study to determine whether certain ocular tissues can make and secrete transferrin. Transferrin content of aqueous and vitreous humors and whole lenses was determined by ELISA. Transferrin secretion by cultured epithelia from lens and ciliary body was also measured. In addition, Northern blots of RNA from cultured lens epithelial cells, ciliary body pigmented and non-pigmented epithelial cells, and from whole iris, ciliary body and retina were probed with riboprobes for Tf mRNA and 18S rRNA. Transferrin made up 23% and 16% of total canine aqueous and vitreous protein. All ocular tissues and cultured cells tested contained mRNA for Tf, however Tf was secreted into the bathing medium from lens epithelial cell cultures, but not from either the pigmented or non-pigmented epithelial cells of the ciliary body Cycloheximide inhibited secretion of Tf from the lens epithelial cells. Lenses from inflamed eyes contained higher levels of Tf than their contralateral controls. This is the first experimental demonstration that an intraocular tissue can make and secrete Tf. Transferrin secretion by the lens may contribute significantly to the IOF content of this important intraocular protein.}, number={6}, journal={EXPERIMENTAL EYE RESEARCH}, author={MCGAHAN, MC and HARNED, J and GORALSKA, M and SHERRY, B and FLEISHER, LN}, year={1995}, month={Jun}, pages={667–673} }
 @article{sherry_blum_1994, title={Multiple viral core proteins are determinants of reovirus-induced acute myocarditis}, volume={68}, number={12}, journal={Journal of Virology}, author={Sherry, B. and Blum, M.A.}, year={1994}, pages={8461–8465} }
 @article{baty_sherry_1993, title={Cytopathogenic effect in cardiac myocytes but not in cardiac fibroblasts is correlated with reovirus-induced acute myocarditis}, volume={67}, number={10}, journal={Journal of Virology}, author={Baty, C.J. and Sherry, B.}, year={1993}, pages={6295–6298} }
 @article{sherry_li_tyler_cullen_virgin_1993, title={Lymphocytes protect against and are not required for reovirus-induced myocarditis}, volume={67}, number={10}, journal={Journal of Virology}, author={Sherry, B. and Li, XY and Tyler, KL and Cullen, JM and Virgin, HW, 4th}, year={1993}, pages={6119–6124} }
 @article{matoba_sherry_fields_smith_1991, title={Identification of the viral genes responsible for growth of strains of reovirus in cultured mouse heart cells.}, volume={87}, ISSN={0021-9738}, url={http://dx.doi.org/10.1172/jci115177}, DOI={10.1172/jci115177}, abstractNote={Viral growth in specific tissue is usually required in order to lead to pathology. Two reovirus isolates (type 1 Lang and type 3 Dearing) differ in their capacity to grow in cultured mouse heart cells. The mammalian reoviruses contain a genome of 10 double-stranded RNA gene segments. By the use of 37 reassortant viruses (consisting of viruses with different combinations of genes derived from the two parents), difference in capacity of different strains to grow in heart cells was mapped to three different genes, all of which encode viral core proteins: the M1 gene (P less than 0.000044); the L1 gene (P = 0.00094); and the L3 gene (P = 0.019). Using the same set of reassortant viruses, the L1 (P = 0.00015) and L3 (P = 0.0065) genes were involved in differences of the ability of viral strains to grow in mouse L cells (fibroblasts), but the M1 gene (P = 0.12) was not. These findings suggest that the M1 gene plays an important and specific role in determining the relative capacity of certain viral strains to grow in the heart. Thus, we have identified viral genes responsible for differing growth capacity in heart muscle cells in culture. These findings provide a novel system for studies of viral myocarditis at a molecular genetic level.}, number={5}, journal={Journal of Clinical Investigation}, publisher={American Society for Clinical Investigation}, author={Matoba, Y and Sherry, B and Fields, B N and Smith, T W}, year={1991}, month={May}, pages={1628–1633} }
 @article{sherry_schoen_wenske_fields_1989, title={Derivation and characterization of an efficiently myocarditic reovirus variant}, volume={63}, number={11}, journal={Journal of Virology}, author={Sherry, B. and Schoen, F.J. and Wenske, E. and Fields, B.N.}, year={1989}, pages={4840–4849} }
 @article{sherry_fields_1989, title={The reovirus M1 gene, encoding a viral core protein, is associated with the myocarditic phenotype of a reovirus variant}, volume={63}, number={11}, journal={Journal of Virology}, author={Sherry, B. and Fields, B.N.}, year={1989}, pages={4850–4856} }
 @article{shepley_sherry_weiner_1988, title={Monoclonal antibody identification of a 100-kDa membrane protein in HeLa cells and human spinal cord involved in poliovirus attachment.}, volume={85}, ISSN={0027-8424 1091-6490}, url={http://dx.doi.org/10.1073/pnas.85.20.7743}, DOI={10.1073/pnas.85.20.7743}, abstractNote={Unique receptor sites for poliovirus are considered to be the primary determinant of the virus' cell and tissue-type specificity. To study the poliovirus-cell interaction, eight monoclonal antibodies that specifically block the cytopathic effects of poliovirus were generated by using HeLa cell preparations as immunogen and a newly developed colorimetric screening assay. Plaque-inhibition assays confirmed the viral specificity of the antibodies, and when one antibody, AF3, was used as a probe in immunoblots of cell membrane preparations, it detected a 100-kDa band in only those cell lines and tissues permissive for poliovirus infection. AF3 also specifically inhibited radiolabeled poliovirus binding to cells. In terms of tissue specificity, AF3 detected the 100-kDa band in membrane preparations from human spinal cord but not in organ homogenates of human kidney or in murine tissue, including the central nervous system. Furthermore, AF3 detected the band in a human-mouse hybrid cell line containing human chromosome 19, which confers permissivity for poliovirus infection, but the antibody did not detect the band in a human chromosome 19-deficient subclone. In an immunohistochemical study of the human brainstem, AF3 stained neurons in the reticular formation and clusters of brainstem neurons, consistent with the known pattern of damage caused by poliovirus infection in the brainstem. Furthermore, AF3 reacted with human peripheral mononuclear cells, consistent with the known replication of poliovirus in Peyer's patches and tonsils. These results strongly suggest that the 100-kDa band detected by antibody AF3 is, or is closely associated with, the poliovirus receptor site.}, number={20}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Shepley, M. P. and Sherry, B. and Weiner, H. L.}, year={1988}, month={Oct}, pages={7743–7747} }
 @article{sherry_mosser_colonno_rueckert_1986, title={Use of monoclonal antibodies to identify four neutralization immunogens on a common cold picornavirus, human rhinovirus 14}, volume={57}, number={1}, journal={Journal of Virology}, author={Sherry, B. and Mosser, A.G. and Colonno, R.J. and Rueckert, R.R.}, year={1986}, pages={246–257} }
 @article{sherry_rueckert_1985, title={Evidence for at least two dominant neutralization antigens on human rhinovirus 14}, volume={53}, number={1}, journal={Journal of Virology}, author={Sherry, B. and Rueckert, R.}, year={1985}, pages={137–143} }
 @article{rossmann_arnold_erickson_frankenberger_griffith_hecht_johnson_kamer_luo_mosser_et al._1985, title={Structure of a human common cold virus and functional relationship to other picornaviruses}, volume={317}, ISSN={0028-0836 1476-4687}, url={http://dx.doi.org/10.1038/317145a0}, DOI={10.1038/317145a0}, number={6033}, journal={Nature}, publisher={Springer Nature}, author={Rossmann, Michael G. and Arnold, Edward and Erickson, John W. and Frankenberger, Elizabeth A. and Griffith, James P. and Hecht, Hans-Jürgen and Johnson, John E. and Kamer, Greg and Luo, Ming and Mosser, Anne G. and et al.}, year={1985}, month={Sep}, pages={145–153} }