Email: Office Phone: 318-675-8122
Laboratory Phone: 318-675-8123
Office Fax: 318-675-5764
Postdoctoral Study, Washington University School of Medicine
Ph.D., Cellular Biology and Biochemistry, 2000, University of Missouri
B.S., Biology, 1995, Southern Illinois University
Major Research Interests:
Pathogenesis of noroviruses, innate immune responses to norovirus infection, and molecular mechanisms of norovirus replication.
Noroviruses are responsible for significant human disease, causing over 90% of nonbacterial epidemic gastroenteritis worldwide. However, the study of these pathogens has been hindered by the lack of a small animal model and tissue culture system. We have recently reported the discovery of the first murine norovirus, MNV-1, and the development of the first norovirus cell culture system. MNV-1 shares pathogenic features with the human noroviruses, at least in immunocompromised animals. A nimals deficient in components of the interferon signaling pathway are strikingly susceptible to acute MNV-1 disease and lethality. Furthermore, primary macrophages and dendritic cells lacking intact Type I interferon signaling are significantly more permissive to MNV-1 infection than are their wild-type counterparts, suggesting that innate immune responses are critical to providing resistance to noroviruses. One goal of our laboratory is to define the interferon-induced antiviral mechanism at both the cellular and the organismal level. Another goal of our laboratory is to define the molecular mechanisms of norovirus replication. Our previous discovery of a cell culture system for MNV-1 allows the study of the norovirus replication cycle in significantly more detail than has heretofore been possible. In experiments defining the molecular intermediates of MNV-1 replication, we have identified a novel lariat RNA structure that is adopted by the MNV-1 genome. We will determine the function of this form of the genome in viral replication and test whether its formation and/or resolution can be targeted as a novel antiviral therapy.
C.E. Wobus, S.M. Karst, A. Krug, K-O. Chang, S.V. Sosnovtsev, G. Belliot, J.M. Mackenzie, K.Y. Green, and H.W. Virgin. 2004. Replication of a Norovirus in cell culture reveals a tropism for dendritic cells and macrophages . PLOS. 2(12): e432.
Karst, S.M. *, C.E. Wobus*, M. Lay, J. Davidson, and H.W. Virgin. 2003. STAT1-dependent innate immunity to a Norwalk-like virus . Science. 299:1575.
Karst, S.M., M.I. Rutz, and T.M. Menees. 2000. The yeast retrotransposons Ty1 and Ty3 require the RNA lariat debranching enzyme, Dbr1p, for efficient accumulation of reverse trancripts . Biochem Biophys Res Comm. 268(1):112.
Karst, S.M., N. Sadeghi, and T.M. Menees. 1999. Cell cycle control of reverse transcriptase activity for the yeast retrotransposon Ty3. Biochem Biophys Res Comm. 254(3):679.