Herbert W. "Skip" Virgin, M.D., Ph.D.

Edward Mallinckrodt Professor and Chair
Pathology and Immunology
Molecular Microbiology

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

Research Abstract:

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 a virus identified through our pathogen discovery efforts: murine norovirus (MNV). 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 immunology, genetics, structure, and pathogenesis; and (6) pathogen discovery.

Selected Publications:

Karst SM, Wobus CE, Lay M, Davidson J and Virgin HW. STAT1-dependent innate immunity to a Norwalk-like virus. Science 2003 Mar 7;299(5612):1575-8.

Wobus CE, Karst SM, Thackray L, Chang K-O, Sosnovtsev SV, Belliot G, Krug A, Mackenzie JM, Green KY, and Virgin HW. Replication of a Norovirus in cell culture reveals a tropism for dendritic cells and macrophages. PLOS Biology 2004 E432. Epub Nov 30 2004.

Barton ES, White DW, Cathelyn JS, Brett-McClellan KA, Engle M, Diamond MS, Miller V, and Virgin HW. Herpesvirus latency confers symbiotic protection from bacterial infection. Nature 2007 May 17;447(7142):326-9.

Cadwell KJ, Liu Y, Brown SL, Miyoshi H, Loh J, Lennerz JK, Kishi C, Kc W, Carrero JA, Hunt S, Stone CD, Brunt EM, Xavier RJ, Sleckman BP, Li E, Mizushima N, Stappenbeck TS and Virgin HW. A unique role for autophagy and the autophagy gene Atg16L1 in murine and human intestinal Paneth cells. Nature 2008 456:259-263.

Cadwell K, Patel KK, Maloney NS, Liu T-C, Ng ACY, Storer CE, Head RD, Xavier R, Stappenbeck TS and Virgin HW. Virus plus susceptibility gene interaction determines intestinal phenotypes of the Crohn`s disease susceptibility gene Atg16L1. Cell 2010 141(7):1135-45.

Last Updated: 9/6/2013 9:58:13 AM

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