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Faculty > Faculty Alphabetical > Herbert Virgin, MD, PhDEdward Mallinckrodt Professor and Chairman, Pathology and Immunology
Director and Principal Investigator, Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research
Professor, Molecular Microbiology
Professor, Medicine
1st Floor Room 1754, West Building
Office: (314) 362-9223
Lab: (314) 362-9224
E-mail: virgin@wustl.edu
Pub Med Search |  |
Research
| | Herbert W. “Skip” Virgin, M.D., Ph.D.
Professor
Department of Pathology and Immunology
Department of Molecular Microbiology
Department of Medicine
Immunology Program
Molecular Microbiology and Microbial Pathogenesis Program
We study issues at the interface between virology and immunology, working from the hypothesis that viruses manipulate the immune response using immunoevasive gene products as the immune response attempts to eradicate the virus. The resulting delicate balance determines the fate of both virus and host, and contributes to both acute and chronic disease. To understand the basis of human diseases of unknown etiology we have an active pathogen discovery program that has identified a number of novel viruses.
Three concepts drive our approach: (1) the simultaneous analysis of immune and viral mechanisms allows novel insights; (2) genetic tests in vivo are necessary to establish mechanisms; and (3) chronic virus infection has profound effects on the physiology of the host. Our experimental models involve infection of mice with a variety of DNA and RNA viruses including murine gammaherpesvirus 68 (ãHV68, MHV-68) and two viruses identified through our pathogen discovery efforts: a novel murine norovirus (MNV) and a novel orthomyxovirus (Quaranfil). Infection of mice with such viruses provides manipulable models for studying the role of viral and host genes in important disease processes.
Current projects include the: (1) cellular and molecular basis of herpesvirus latency and tumorigenesis; (2) mechanisms of interferon-ã (IFNã) and IFNáâ in control of actue and chronic infection; (3) role of autophagy in IFNã function and immunity; (4) role of viruses and autophagy proteins in intestinal immunity and barrier function in Crohn’s disease; (5) norovirus and orthomyxovirus immunology, structure, and pathogenesis; and (6) pathogen discovery.
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1. Karst, S.M., Wobus, C. E., Lay, M., Davidson, J., and H. W. Virgin. STAT1-dependent innate immunity to a Norwalk-like virus. 2003. Science. Mar 7;299(5612):1575-8.
2. Wobus, C. E., S. M. Karst, L. Thackray, K.-O. Chang, S. V. Sosnovtsev, G. Belliot, A. Krug, J. M. Mackenzie, K. Y. Green, and H. W. Virgin. Replication of a Norovirus in cell culture reveals a tropism for dendritic cells and macrophages. 2004. PLOS Biology. E432. Epub Nov 30 2004.
3. Barton. E. S., D. W. White, J. S. Cathelyn, K. A. Brett-McClellan, M. Engle, M. S. Diamond, V. Miller, and H. W. Virgin. Herpesvirus latency confers symbiotic protection from bacterial infection. 2007. Nature. May 17;447(7142):326-9.
4. Zhao, Z., B. Fux, M. Goodwin, I. R. Dunay, D. Strong, B. C. Miller, K. Cadwell, M. Delgado-Vargas, M. Ponpuak, K. G. Green, R. E. Schmidt, N. Mizushima, V. Deretic, L. D. Sibley, and H. W. Virgin. Autophagosome-independent essential function for the autophagy protein Atg5 in cellular immunity to intracellular pathogens. 2008. Cell Host and Microbe. 4(5):458-69. PMID 18996346.
5. Cadwell, K., J. Y. Liu, S. L. Brown, H. Miyoshi, J. Loh, J. K. Lennerz, C. Kishi, W. Kc, J. A. Carrero, S. Hunt, C. D. Stone, E. M. Brunt, R. J. Xavier, B. P. Sleckman, E. Li, N. Mizushima, T. S. Stappenbeck, and H. W. Virgin, A unique role for autophagy and the autophagy gene Atg16L1 in murine and human intestinal Paneth cells. 2008. Nature. 456:259-263. PMID 18849966.
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Editorial Responsibilities
| | 2008 - Present | Editorial Board | Current Topics in Microbiology and Immunology | | 2006 - Present | Editorial Board | Cell Host & Microbe | | 2005 - Present | Editorial Board | Virology | | 2005 - Present | Associate Editor | Public Library of Science Pathogen | | 2004 - Present | Editorial Board | Autophagy | | 2003 - Present | Editorial Board | Public Library of Science Biology | | 2000 - Present | Editorial Board | Journal of Virology |
Service to the Department
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Service to the University
| | 2009 - Present | Director and Principal Investigator, Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research | | 2006 - Present | Research Affairs Committee | | 2006 - Present | Siteman Cancer Center Leadership Council, Washington University | | 2006 - Present | Faculty Practice Plan Clinical Practice Committee | | 2006 - Present | University Strategic Planning Committee | | 2006 - Present | Medical Executive Committee, Barnes-Jewish Hospital | | 2006 - Present | Preclinical Chiefs Committee, Washington University School of Medicine | | 2003 - Present | Institutional Representative for American Society of Clinical Investigators (ASCI) | | 2003 - Present | Advisory Committee and Inflammation Franchise Director, Washington University/Pfizer Biomedical Program | | 1999 - Present | Immunology Program Steering Committee |
Diagnostic Expertise
| | Pathogen Discovery |
Selected Publications
| | Virgin HW, Wherry EJ, Ahmed R. Redefning Chronic Viral Infection. Cell July 10; 138(1): 30-50, 2009 Abstract
| | Virgin HW, Levine B. Autophagy Genes in Immunity. Nature Immunology 10(5): 461-70, 2009 Abstract
| | Chachu KA, LoBue AB, Strong DW, Baric RS, Virgin HW. Immune Mechanisms responsible for vaccination against and clearance of mucosal and lymphatic norovirus infection. PLoS Pathogen 4(12)e1000236, 2008 Abstract
| | McCartney SA, Thackray LB, Gitlin L, Virgin HW, Colonna M. MDA-5 Recognition of a Murine Norovirus. PLoS Pathogen 4(7):e1000108, 2008 Abstract
| | Cadwell K, Liu JY, Brown SL, Miyoshi H, Loh J, Lennerz JK, Kishi C, Kc W, Carrero JA, Hunt SA, Stone CD, Brunt EM, Xavier RJ, Sleckman BP, Li E, Mizushima N, Stappenbeck TS, Virgin HW. A key role for autophagy and the autophagy gene Atg16L1 in murine and human intestinal Paneth cells. Nature 456:259-263, 2008 Abstract
| | Zhao Z, Fux B, Goodwin M, Dunay IR, Strong D, Miller BC, Cadwell K, Delgado-Vargas M, Ponpuak N, Green KG, Schmidt RE, Mizushima N, Deretic V, Sibley LD, Virgin HW. Autophagosome-independent essential function for the autophagy protein Atg5 in cellular immunity to intracellular pathogens. Host and Microbe 4(5):458-69, 2008 Abstract
| | Frias-Staheli N, Giannakopoulos NV, Kikkert M, Taylor SL, Bridgen A, Paragas J, Richt JA, Schmaljohn CS, Lenschow DJ, Snijder EJ, Garcia-Sastre A, Virgin, HW. Ovarian tumor domain-containing viral proteases evade ubiquitin- and ISG15-dependent innate immune responses. Cell Host and Microbe 2(26): 404-416, 2007 Abstract
| | Barton ES, White DW, Cathelyn JS, Brett-McClellan KA, Engle M, Diamond MS, Miller VL, Virgin HW. Herpesvirus latency confers symbiotic protection from bacterial infection. Nature 447(7142):326-329, 2007 Abstract
| | Lenschow DJ, Lai C, Frias-Staheli N, Giannakopoulos NV, Lutz A, Wolff T, Osiak A, Levine B, Schmidt RE, Garcia-Sastre A, Leib DA, Pekosz A, Knobeloch KP, Horak I, Virgin HW. IFN-stimulated gene 15 functions as a critical antiviral molecule against influenza, herpes, and Sindbis viruses. PNAS 104(4):1371-1376, 2007 Abstract
| | Ward VK, McCormick CJ, Clarke IN, Salim O, Wobus CE, Thackray LB, Virgin HW, Lambden PR. Recovery of infectious murine norovirus using pol II-driven expression of full-length cDNA.. PNAS 104(26):11050-5, 2007 Abstract
| | Tarakanova V L, Leung-Pineda V, Hwang S, Yang CW, Matatall K, Basson M, Sun R, Piwnica-Worms H, Sleckman BP, Virgin HW. Herpesvirus kinase initiates DNA damage response by inducing phosphorylation of H2AX to foster viral replication.. Cell Host and Microbe 1:275-286., 2007 Abstract
| | Tarakanova VL, Leung-Pineda V, Hwang S, Yang CW, Matatall K, Basson M, Sun R, Piwnica-Worms HP, Sleckman BP, Virgin HW. Gamma-herpesvirus kinase actively initiates DNA damage response by inducing phosphorylation of H2AX to foster viral replication. Cell Host and Microbe 1:275-286, 2007 Abstract
| | Braaten DC, McClellan JS, Messaoudi I, Tibbetts SA, McClellan KB, Nikolich-Zugich J, Virgin HW. Effective control of chronic gamma-herpesvirus infection by unconventional MHC Class Ia-independent CD8 T cells. PLoS Pathogen 2(5):e37, 2006 Abstract
| | McClellan KB, Gangappa S, Speck SH, Virgin HW. Antibody-independent control of gamma-herpesvirus latency via B cell induction of anti-viral T cell responses. PLoS Pathogen 2(6):e58, 2006 Abstract
| | Loh J, Huang Q, Petros AM, Nettesheim D, van Dyk LF, Labrada L, Speck SH, Levine B, Olejniczak ET, Virgin HW 4th. A surface groove essential for viral Bcl-2 function during chronic infection in vivo. PLoS Pathogen 1(1):e10, 2005 Abstract
| | Wobus CE, Karst SM, Thackray LB, Chang KO, Sosnovtsev SV, Belliot G, Krug A, Mackenzie JM, Green KY, Virgin HW. Replication of Norovirus in cell culture reveals a tropism for dendritic cells and macrophages. PLoS Biol 2(12):e432, 2004 Abstract
| | Wang F, Ma Y, Barrett JW, Gao X, Loh J, Barton E, Virgin HW, McFadden G. Disruption of Erk-dependent type I interferon induction breaks the myxoma virus species barrier. Nat Immunol. 5(12):1266-74, 2004 Abstract
| | Popkin DL, Watson MA, Karaskov E, Dunn GP, Bremner R, Virgin HW. Murine cytomegalovirus paralyzes macrophages by blocking IFNgamma-induced promoter assembly. PNAS 100:14309-14314, 2003 Abstract
| | Karst SM, Wobus CE, Lay M, Davidson J, Virgin HW. STAT1-Dependent Immunity to a Norwalk-Like Virus. Science 299:1575-1578, 2003 Abstract
| | Lybarger L, Wang X, Harris MR, Virgin HW, Hansen TH. Virus subversion of the MHC class I peptide-loading complex. Immunity 18:121-130, 2003 Abstract
| | Kapadia SB, Levine B, Speck SH, Virgin HW. Critical role of complement and viral evasion of complement in acute, persistent, and latent gamma-herpesvirus infection. Immunity 17:143-155, 2002 Abstract
| | Alexander JM, Nelson CA, van Berkel V, Studts JM, Brett TJ, Speck SH, Handel TM, Virgin HW, Fremont D. Structural basis of chemokine sequestration by a herpesvirus decoy receptor. Cell 111:343-356, 2002 Abstract
| | Van Berkel V, Levine B, Goldman JE, Speck SH, Virgin HW. Critical role for a high affinity chemokine binding protein in lethal meningitis caused by a gamma-herpesvirus. J Clin Invest 109:905-914, 2002 Abstract
| | Gangappa S, van Dyk LF, Jewett T, Speck SH, Virgin HW. Identification of the in vivo role of a viral bcl-2. J Exp Med 195:931-940, 2002 Abstract
| | Talloczy Z, Jiang W, Virgin HW, Leib DA, Scheuner D, Kaufman RJ, Eskelinen EL, Levine B. Regulation of starvation- and virus-induced autophagy by the eIF-2alpha kinase signaling pathway. PNAS 99:190-195, 2002 Abstract
| | Gil MP, Bohn E, O'Guin AK, Ramana CV, Levine B, Stark R, Virgin HW, Schreiber RD. Biological consequences of Stat1-independent IFN signaling. PNAS 98:6680-6685, 2001 Abstract
| | Presti MP, Popkin DL, Connick M, Paetzold S, Virgin HW. Novel cell type specific antiviral mechanism of IFNgamma action in macrophages. J Exp Med 193:483-496, 2001 Abstract
| | Dal Canto AJ, Swanson PE, O'Guin AK, Speck SH, Virgin HW. Interferon-gamma action in the media of the great elastic arteries, a novel immunoprivileged site. J Clin Invest 107:15-22, 2001 Abstract
| | Leib DA, Machalek MA, Williams BR, Silverman RH, Virgin HW. Specific phenotypic restoration of an attenuated virus by knockout of a host resistance gene. PNAS 97:6097-6101, 2000 Abstract
| | Leib DA, Harrison TE, Laslo KM, Machalek MA, Moorman NJ, Virgin HW. Interferons regulate the phenotype of wild-type and mutant herpes simplex viruses in vivo. J Exp Med 189:663-672, 1999 Abstract
| | Presti RM, Pollock JL, Dal Canto AJ, O'Guin AK, Virgin HW. Interferon-gamma regulates acute and latent murine cytomegalovirus infection and chronic disease of the great vessels. J Exp Med 188:577-588, 1998 Abstract
| | Heise MT, Connick M, Virgin HW. Murine cytomegalovirus inhibits interferon-gamma-induced antigen presentation to CD4 T cells by macrophages via regulation of expression of MHC class II associated genes. J Exp Med 187:1037-1046, 1998 Abstract
| | Weck KE, Dal Canto AJ, Gould JD, O'Guin AK, Roth KA, Saffitz JE, Speck SH, Virgin HW. Murine gamma-herpesvirus-68 causes severe large vessel arteritis in mice lacking interferon-gamma responsiveness: a new model for virus induced vascular disease. Nat Med 3:1346-1353, 1997 Abstract
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Current Trainees
| | Monique Bruinsma | | Susan Canny | | Megan Goodwin | | Nicole Maloney | | Brian Miller | | David Strong | | Ken Cadwell, PhD | | Seungmin Hwang, PhD | | Amelia Pinto, PhD | | Rachel Presti, MD, PhD | | Tiffany Reese, PhD | | Larissa Thackray | | Doug White, MD | | Erin Willert, PhD | | Zijiang Zhao, PhD |
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