Dr. Herbert ‘Skip’ Virgin is the Edward Mallinckrodt Professor and Chair of the Department of Pathology and Immunology at the Washington University School of Medicine in Saint Louis, Missouri, USA. He also serves as the Principal Investigator for the Center of Excellence for Translational Research funded by the NIH to develop autophagy-targeted broad-spectrum antimicrobial agents.
Dr. Virgin received his A.B. from Harvard College in 1977 and his M.D. and Ph.D. from Harvard Medical School in 1985. His Ph.D. thesis was done in the laboratory of Dr. Emil Unanue studying interferon-mediated resistance to Listeria monocytogenes. He completed training in internal medicine and infectious diseases and postdoctoral training in viral genetics and pathogenesis with Dr. Bernard Fields before joining the faculty at Washington University School of Medicine in 1991. Dr. Virgin is a member of the American Society for Clinical Investigation, a Fellow of the American Association for the Advancement of Science, a member of the American Association of Physicians, and a Fellow of the American Academy of Microbiology. He serves on the editorial boards of PLoS Biology, Cell Host and Microbe, and mBio and is a member of the Board of Reviewing Editors of Science. He has contributed reviews in Cell, Nature, Nature Immunology, and Cell Host and Microbe, on autophagy and immunity, HIV immunity and vaccination, noroviruses, and the virome and virus-plus-susceptibility gene interaction concepts.
The Virgin laboratory uses genetic, structural, computational, and sequencing methods to define the mechanisms controlling viral pathogenesis and immunity in vivo. They have identified the physiologic role and molecular mechanisms of several RNA and DNA virus immune evasion molecules including an H2AX kinase, a complement regulatory protein, a chemokine binding protein, a viral Bcl-2, a viral cyclin, and a viral de-ubiqitinase. On the host side, they have defined specific effector mechanisms of interferon responses, including identifying ISG15 as a key antiviral molecule, and demonstrated the role of cGAS in RNA and DNA virus infection. They formulated and proved the hypothesis that cassettes of autophagy proteins exert non-degradative functions that contribute to IFN-γ-mediated control of viral and parasite replication, and were the first to show that autophagy proteins function in macrophage secretion of cellular proteases.
By studying virus-host interactions they defined the genetic test of host complementation to identify molecular mechanisms of immune evasion in vivo, showed that viral species-specificity is conferred by host genes in the innate immune system, and demonstrated that herpesvirus infection confers immune-mediated symbiotic advantages to the host in a manner dependent on viral genes required for latency. They found that the autophagy protein Atg16L1 plays a key role in both mouse and human intestinal Paneth cells, and defined the concept that viruses can control intestinal disease pathogenesis through virus-plus-susceptibility gene interactions. Recent studies of co-infection revealed that helminth infection reactivates a murine gammaherpesvirus from latency through a novel mechanism in which a viral promoter responds to host cytokines, and that this mechanism functions for the human Kaposi's sarcoma-associated herpesvirus.
By studying the metagenome they discovered the first murine norovirus and developed the first culture system for a norovirus. They have developed next-generation sequencing and bioinformatic tools and used them to identify the constituents of the mammalian virome and to show that the enteric virome is substantially expanded in macaques with SIV infection. These emergent novel viruses may contribute to AIDS enteropathy.