Christiane Wobus, Ph.D.
Department of Microbiology and Immunology firstname.lastname@example.org
Mechanisms of norovirus – host interactions with macrophages, dendritic cells, and the gastrointestinal tract
The Wobus lab is interested in mechanisms of norovirus - host interactions in vitro and in vivo.
Human noroviruses are the major cause of nonbacterial epidemic gastroenteritis worldwide resulting in substantial morbidity and economic loss. They cause an estimated 23 million cases of gastroenteritis per year in the USA alone and are frequent visitors to cruise ships, hospitals, daycare centers and other places were crowds gather. However, despite the importance for public health, human norovirus research has been severely hampered by the lack of a small animal model and in vitro replication system. Therefore, little or no information is available in many areas of norovirus biology and no directed disease prevention and control strategies exist for these viruses.
With our discovery of the first murine norovirus (MNV-1) and hence the availability of a small animal model, the development of the first in vitro culture system and reverse genetics system for a norovirus, we have a unique system to begin a detailed analysis of different aspects of norovirus biology. Current studies in the lab are focused on: 1) mechanisms of MNV transport across the intestinal epithelial barrier, 2) identification of MNV receptor(s) and their binding site(s) on the MNV capsid, and 3) investigating the role of cellular deubiquitinases during MNV infection in macrophages and dendritic cells.
We recently developed the first small animal model for human noroviruses and are expanding our studies to these viruses. Our work with human noroviruses focuses on: 1) identifying cellular and viral factors of host susceptibility in the mouse model, and 2) developing methods to cultivate these viruses.
Representative Recent Publications
Taube, S., Rubin, J. R., Katpally, U., Smith, T. S., Kendall, A., Stuckey, J. A., and Wobus, C. E. (2010) High Resolution X-Ray Structure and Functional Analysis of the Murine Norovirus (MNV)-1 Capsid Protein Protruding (P) Domain. Journal of Virology 84, 5695-705.
Kim, Y.G., Park, J.H., Reimer, T., Baker, D.P., Kawai, T., Kumar, H., Akira, S., Wobus C., Núñez, G. (2011) Viral infection augments nod1/2 signaling to potentiate lethality associated with secondary bacterial infections. Cell Host Microbe 9, 496-507.
Perry, J.W., Ahmed, M., Chang, K.-O., Donato, N.J., Showalter, H.D., and Wobus, C.E. (2012) Antiviral Activity of a Small Molecule Deubiquitinase Inhibitor Occurs via Induction of the Unfolded Protein Response. PLoS Pathogens 8:e1002783.
Elftman, M.D., Gonzalez-Hernandez, M.B., Kamada, N., Perkins, C., Henderson, K.S., Núñez, G., and Wobus, C.E. (2013) Multiple effects of dendritic cell depletion on murine norovirus infection. Journal of General Virology 94:1761-8.
Taube, S*., Kolawole, A.O.*, Höhne, M., Wilkinson, J.E., Handley, S.A., Perry, J.W., Thackray, LB., Akkina, R., Wobus, C.E. (2013) A Mouse Model for Human Norovirus. mBIO 4:e00450-13.
Kolawole, A. O., Li, M., Xia, C., Fischer, A. E., Giacobbi, N. S., Rippinger, C. M., Proescher, J. B., Wu, S. K., Bessling, S. L., Gamez, M., Yu, C., Zhang, R., Mehoke, T. S., Pipas, J. M., Wolfe, J. T., Lin, J. S., Feldman, A. B., Smith, T. J., and Wobus, C. E. (2014) Flexibility in surface exposed loops in the virus capsid mediates escape from antibody neutralization. Journal of Virology 88:4543-57.
Gonzalez-Hernandez, M.B., Liu, T., Payne, H.C., Stencel-Baerenwald, J., Ikizler, M., Yagita, H., Dermody, T.S., Williams, I.R., Wobus, C.E. (2014) Efficient norovirus and reovirus replication in the mouse intestine requires microfold (M) cells. Journal of Virology 88:6934-6943.
Karst, S.M., Wobus, C.E., Goodfellow, I.G., Green, K.Y., Virgin, H.W. (2014) Advances in Norovirus Biology. Cell Host Microbe 15:668-680. (Review)