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Faculty > Faculty By Appointment > Herbert Virgin IV, MD, PhD

Edward Mallinckrodt Professor and Chairman,
Department, Pathology and Immunology
Professor, Microbiology
Professor, Medicine
Room 8849, 8th Floor, Clinical Sciences Research 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

Our laboratory focuses on the host/pathogen/symbiote interface paying particular attention to mechanisms that operate in vivo. We study host pathways, such as autophagy and interferon responses, identified as important for human disease susceptibility or resistance in mice and humans. Our primary interest has been in chronic virus infection and the virome, but we also study bacterial, helminth, and apicomplexan pathogens and commensals. We use genetic, computational, next-generation sequencing, and structural methods to define the mechanisms and pathways that control disease pathogenesis and immunity. We defined the genetic test of host complementation to identify molecular mechanisms of immune evasion in vivo, discovered the first murine norovirus, developed the first culture system for a norovirus, and demonstrated that herpesviruses can confer symbiotic advantages to their hosts. In recent work we have focused on the role of interferon and both canonical and non-degradative functions of autophagy proteins in innate and adaptive immunity, pathogen resistance, and protein secretion. We have developed next generation sequencing technologies to define the virome, and used them to identify potential physiologic roles for the virome in diseases including inflammatory bowel disease and AIDS enteropathy. We have trained a number of young investigators including Mark Heise (UNC, tenure); Karen Weck (UNC); Sharookh Kapadia (Genetech); Barbara Haller (UCSF); Linda van Dyk (Univ. Colorado, tenure), Scott Tibbetts (Univ. Florida); Stephanie Karst (Univ. Florida); Felipe Suarez (Université Paris Descartes), Linda Van Dyk (Univ. Colorado, tenure); Christiane Wobus (Univ. Michigan, tenure); Nat Moorman (UNC); Rachel Presti (Washington University); Doug White (Gundersen Health System & Univ. of Wisconsin); Vera Tarakanova (Medical College of Wisconsin); Erik Barton (Wake Forest); Shivaprakash Gangappa (CDC); Deborah Lenschow (Washington Univ., tenure); Ken Cadwell (NYU School of Medicine), Dan Popkin (Case Western), and Seungmin Hwang (Univ. Chicago).

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. 141:1135-45.
6. Handley, S., L. B. Thackray, G. Zhao, R. Presti, A. Miller, L. Droit, P. Abbink, L. F. Maxfield, A. Kambal, E. Duan, J. Kramer, S. C. Macri, S. R. Permar, J. E. Schmitz, K. Mansfield, J. Brenchley, R. S. Veazey, T. S. Stappenbeck, D. Wang, D. H. Barouch, and H. W. Virgin. Pathogenic simian immunodeficiency virus infection is associated with significant expansion of the enteric virome. 2012. Cell. 151:253-266.
7. Reese, T. A., B. S. Wakeman, H. S. Choi, M. M. Hufford, S. C.C. Huang, X. Zhang, M. D. Buck, A. Jezewski, A. Kambal, C. Y. Liu, G. Goel, P. J. Murray, R. J. Xavier, M. H. Kaplan, R. Renne, S. H. Speck, M. N. Artyomov, E. J. Pearce, and H. W. Virgin. Helminth Co-infection Reactivates Gammaherpesvirus Infection Through Viral Promoter-targeted Cytokine Competition. 2014. Science. Published online 26 June 2014 [DOI:10.1126/science.1254517]

Editorial Responsibilities

2010 - PresentBoard of Reviewing EditorsScience
2010 - PresentEditorial BoardmBio
2006 - PresentEditorial BoardCell Host & Microbe
2005 - PresentEditorial BoardPLoS Biology

Service to the Department


Service to the University

2006 - PresentSiteman Cancer Center Leadership Council, Washington University
2006 - PresentFaculty Practice Plan Clinical Practice Committee
2006 - PresentResearch Affairs Committee
2006 - PresentMedical Executive Committee, Barnes-Jewish Hospital
2006 - PresentPreclinical Chiefs Committee, Washington University School of Medicine
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

Schoggins, J.W. D. A. MacDuff, N. Imanaka, M. D. Gainey, B. Shrestha, ... , A. Garcia-Sastre, V. Racaniello, E. J. Snijder, W. M. Yokoyama, M. S. Diamond, H. W. Virgin, C. M. Rice. Pan-viral specificity of IFN-induced genes reveals new roles for cGAS in innate immunity. Nature. 505:691-5, 2014 Abstract

Reese, T. A., B. S. Wakeman, H. S. Choi, M. M. Hufford, S. C.C. Huang, X. Zhang, M. D. Buck, A. Jezewski, A. Kambal, C. Y. Liu, G. Goel, P. J. Murray, R. J. Xavier, M. H. Kaplan, R. Renne, S. H. Speck, M. N. Artyomov, E. J. Pearce, and H. W. Virgin. Helminth Co-infection Reactivates Gammaherpesvirus Infection Through Viral Promoter-targeted Cytokine Competition. Science. In Press., 2014 Abstract

Canny, S. P., T. A. Reese, L. S. Johnson, X. Zhang, A. Kambal, E. Duan, C.Y. Liu, and H. W. Virgin.. Pervasive transcription of a herpesvirus genome generates functionally important RNAs. mBio. 5(2):e01033-13, 2014 Abstract

Choi, J., S. Park, S. B. Biering, E. Selleck, C. Y. Liu, X. Zhang, N. Fujita, T. Saitoh, S. Akira, T. Yoshimori, L. D. Sibley, S. Hwang, H. W. Virgin. The Parasitophorous Vacuole Membrane of Toxoplasma gondii is Targeted for Disruption by Ubiquitin-like Conjugation Systems of Autophagy. Immunity. 40(6)924-35, 2014 Abstract

Virgin, H. W.. The virome in mammalian physiology and disease. Cell. 157(1):142-150, 2014 Abstract

Handley, S., L. B. Thackray, G. Zhao, R. Presti, A. Miller, L. Droit, P. Abbink, L. F. Maxfield, A. Kambal, E. Duan, J. Kramer, S. C. Macri, S. R. Permar, J. E. Schmitz, K. Mansfield, J. Brenchley, R. S. Veazey, T. S. Stappenbeck, D. Wang, D. H. Baro. Pathogenic simian immunodeficiency virus infection is associated with significant expansion of the enteric virome.. Cell. 151:253-266, 2012 Abstract

Virgin, H. W., and J. A. Todd. Metagenomics and Personalized Medicine. Cell. 147(1):44-56, 2011 Abstract

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

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. Cell. 141(7): 1135-45, 2010 Abstract

Virgin HW, Wherry EJ, Ahmed R. Redefning Chronic Viral Infection. Cell 138: 30-50, 2009 Abstract

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

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

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

Karst SM, Wobus CE, Lay M, Davidson J, Virgin HW. STAT1-Dependent Immunity to a Norwalk-Like Virus. Science 299:1575-1578, 2003 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

Assistant Professor of Pathology and Immunology:

    Scott Handley, PhD
    Guoyan Zhao, PhD

Instructor of Pathology and Immunology:

    Donna MacDuff, PhD
    Tiffany Reese, PhD

Fellows:

    Megan Baldridge, MD, PhD
    Cynthia Johnson, MD, PhD
    Brian Keller, MD, PhD
    Qun Lu, PhD
    Timothy Nice, PhD
    Jason Norman, PhD
    Robert Orchard, PhD
    Anthony Orvedahl, MD, PhD
    Veronika Redman, PhD
    Craig Wilen, MD, PhD

Students:

    Broc McCune, BS
    Sunmin Park, MS
    Christine Yokoyama, BA