Virgin Lab Research

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. Analysis of these issues is key to understanding chronic diseases caused by viruses. The diseases that we study include lymphoma induced by γ-herpesviruses, vascular disease including atherosclerosis induced by herpesviruses, and enteric disease induced by noroviruses. Lastly, we are searching for novel human pathogens using molecular and classical methods.

Two concepts drive our approach: (1) the simultaneous analysis of immune and viral mechanisms allows novel insights; and (2) genetic tests in vivo are necessary to establish mechanisms. The experimental models used in the lab are infection of mice with the herpesviruses murine cytomegalovirus (MCMV), herpes simplex virus (HSV), and murine gammaherpesvirus 68 (γHV68). In addition, we have found a novel Norwalk-like virus (norovirus, named MNV-1) in mice that is under intensive study.

HSV, MCMV, and γHV68 establish latency despite active immunity, contributing to their capacity to cause chronic diseases. MCMV causes vasculitis and atherosclerosis. γHV68 induces lymphoma, vasculitis, and atherosclerosis. MNV-1 causes pneumonia and gastoenteritis. Infection of mice with these viruses provids manipulable models for studying the role of viral and host genes in important disease processes.

Current projects include: (1) the cellular and molecular basis of herpesvirus latency; (2) the role of interferon-γ (IFNγ), TNF, perforin, granzymes, B cells, antibody, and T cells in herpesvirus latency; (3) vaccination against latency; (4) molecular mechanisms of IFNγ anti-viral action; (5) herpesvirus tumor induction; (6) herpesvirus-induced vascular disease and atherosclerosis; (7) herpesvirus immune evasion proteins that block antigen presentation and IFN signaling; (8) herpesvirus regulators of apoptosis including the γHV68 v-bcl-2; and (9) norovirus immunology, structure, and pathogenesis; and (10) pathogen discovery.