My 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. 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. Our discovery of murine norovirus 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, have given us 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 transcytosis across intestinal epithelial monolayers in vitro and in vivo, 2) the role of dendritic cells during MNV infection in vivo, 3) identification of MNV receptor(s), 4) defining the receptor binding site(s) on the MNV capsid, and 5) investigating the role of cellular deubiquitinases during MNV infection in macrophages and dendritic cells. Recently, we also started to expand our studies to human noroviruses using the currently available techniques (e.g. replicon system, virus-like particles) to investigate interactions at the intestinal epithelium and the role of deuqbiuitinases.
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.
Gonzalez-Hernandez, M. B., Lui, T., Blanco, L. P., Auble, H., Payne, H. C., Wobus, C. E. (2013) Murine Norovirus Transcytosis Across an In Vitro Polarized Murine Intestinal Epithelial Monolayer is Mediated by M-like Cells. Journal of Virology 87:12685-93.
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.
Kolawole, A.O., Xia, C., Li, M., Gamez, M., Yu, C., Rippinger, C.M., Yucha, R.E., Smith, T.J., Wobus, C.E. (2014) Newly isolated monoclonal antibodies broaden neutralizing epitope in murine norovirus. Journal of General Virology 95:1958-68.
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)
Jones, M.K., Watanabe, M., Zhu, S., Graves, C.L., Keyes, L.R., Grau, K.R., Gonzalez-Hernandez, M.B., Iovine, N.M., Wobus, C.E., Vinjé, J., Tibbetts, S.A., Wallet, S.M., Karst, S.M. (2014) Enteric bacteria promote human and mouse norovirus infection of B cells. Science 346: 755-759.
Fischer, A.E., Wu, S.K., Proescher, J.B., Rotem, A., Chang, C.B., Zhang, H., Tao, Y., Mehoke, T.S., Thielen, P.M., Kolawole, A.O., Smith, T.J., Wobus, C.E., Weitz, D.A., Lin, J.S., Feldman, A.B., Wolfe, J.T. (2014) A high-throughput drop microfluidic system for virus culture and analysis. Journal of Virological Methods 213C:111-117.
Zhang, H., Cockrell, S.K., Kolawole, A.O., Rotem, A., Serohijos, A.W., Chang, C.B., Tao, Y., Mehoke, T.S., Han, Y., Lin, J.S., Giacobbi, N.S., Feldman, A.B., Shakhnovich, E., Weitz, D.A., Wobus, C.E., Pipas, J.M. (2015) Isolation and analysis of rare norovirus recombinants from co-infected mice using drop-based microfluidics. Journal of Virology [Epub ahead of print]
Karst, S.M. and Wobus, C.E. (2015) Viruses in Rodent Colonies: Lessons learned from murine noroviruses. Annual Review of Virology 2:5.1-5.24.