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Research > Faculty Alphabetical > Herbert Virgin IV, MD, PhD

Edward Mallinckrodt Professor and Chair, Pathology and Immunology
Professor of Molecular Microbiology
Professor, Medicine
1st Floor Room 1754, West Building
Office: (314) 362-9223
Lab: (314) 362-9224
E-mail: virgin@wustl.edu
Web-site: http://pathology.wustl.edu/labs/virgin/
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 (HV68, 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- (IFN) and IFN in control of actue and chronic infection; (3) role of autophagy in IFN function and immunity; (4) role of viruses and autophagy proteins in intestinal immunity and barrier function in Crohns disease; (5) norovirus immunology, genetics, 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. 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.
5. Cadwell, K., K. K. Patel, N. S. Maloney, T.-C. Liu, A. C. Y. Ng, C. E. Storer, R. D. Head, R. Xavier, T. S. Stappenbeck, and H. W. Virgin. Virus plus susceptibility gene interaction determines intestinal phenotypes of the Crohn's disease susceptibility gene Atg16L1. 2010. Cell. In Press.



Editorial Responsibilities

2008 - PresentEditorial BoardCurrent Topics in Microbiology and Immunology
2006 - PresentEditorial BoardCell Host & Microbe
2005 - PresentEditorial BoardVirology
2004 - PresentEditorial BoardAutophagy

Service to the Department


Service to the University

2009 - PresentDirector and Principal Investigator, Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research
2006 - PresentResearch Affairs Committee
2006 - PresentSiteman Cancer Center Leadership Council, Washington University
2006 - PresentFaculty Practice Plan Clinical Practice Committee
2006 - PresentMedical Executive Committee, Barnes-Jewish Hospital
2006 - PresentPreclinical Chiefs Committee, Washington University School of Medicine
2003 - PresentAdvisory Board Washington University/Pfizer Biomedical Program
1999 - PresentImmunology Program Steering Committee

DBBS Graduate Program Affiliation

Immunology Program
Molecular Microbiology and Microbial Pathogenesis Program
Human and Statistical Genetics Program

Diagnostic Expertise

Pathogen Discovery

Selected Publications

Cadwell KK, Patel K, Maloney NS, Liu TC, Ng ACY, Storer CE, Head RD, Xavier R, Stappenbeck TS, Virgin HW. Virus plus susceptibility gene interaction determines intestinal phenotypes of the Crohn[]s disease susceptibility gene Atg16L1. Cell In Press, 2010 Abstract

Virgin HW, Walker BD. Immunology and the elusive AIDS vaccine. Nature 464:224-231, 2010 Abstract

Virgin HW, Levine B. Autophagy Genes in Immunity. Nature Immunology 10: 461-70, 2009 Abstract

Virgin HW, Wherry EJ, Ahmed R. Redefning Chronic Viral Infection. Cell 138: 30-50, 2009 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. Cell Host and Microbe 4:458-69, 2008 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:e1000236, 2008 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 447:326-329, 2007 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: 404-416, 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 104:1371-1376, 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:e37, 2006 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:e432, 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

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

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

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


Current Trainees

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Megan Baldridge, MD, PhD
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Christine Yokoyama
Steve Johnson, PhD
Susan Canny
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Past Trainees

Postdoctoral Fellows
Tiffany Reese, PhD