Christiane Wobus, Ph.D.
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.
1. The role of dendritic cells during MNV pathogenesis
Ongoing work in the laboratory has shown that microfold (M) cells within the intestinal epithelium are critical during MNV and reovirus pathogenesis. Furthermore, MNV can cross an intestinal epithelial monolayer in vitro via M-like cells without disrupting tight junctions by an intracellular endocytic pathway called transcytosis. Our goal is to identify cellular factors required during this process and to expand the in vitro studies to include studies with human norovirus virus-like particles (a non-infectious form of the virus comprised only of the virus capsid).
The ubiquitin system plays a fundamental role during many cellular processes, including cytokine signaling. Deubiquitinases are a critical regulator of the ubiquitin cycle but relatively little is known regarding their functions. We have discovered a small molecule inhibitor of a select set of cellular deubiquitinases that inhibits replication of MNV and the human norovirus Norwalk virus. Ongoing studies are focused on identifying the complete set of target proteins targeted by the small molecule inhibitor, the anti-viral mechanism of action of the small molecule, and the function of these deubiquitinases in macrophages and dendritic cells.
Representative Recent Publications
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 (accepted for publication)
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.
Taube, S., Perry, J. W., McGreevy, E., Yetming, K., Perkins, C., Henderson, K., Wobus, C. E. (2012) Murine noroviruses (MNV) bind glycolipid and glycoprotein attachment receptors in a strain-dependent manner. Journal of Virology 86:5584-93.
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. and Wobus, C. E. (2010) Endocytosis of Murine Norovirus 1 (MNV-1) into murine macrophages is dependent on dynamin II and cholesterol. Journal of Virology 84, 6163–6176
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
Perry, J., Taube, S., Wobus, C. E. (2009) Murine Norovirus-1 entry into permissive macrophages and dendritic cells is pH-independent. Virus Research 43, 125-9.
Taube, S., Perry, J. W., Yetming, K., Patel, S. P., Auble, H., Shu, L., Nawar, H. F., Lee, C. H., Connell, T. D., Shayman, J., Wobus, C. E. (2009) Ganglioside-linked terminal sialic acid moieties on murine macrophages function as attachment receptors for Murine Noroviruses (MNV). Journal of Virology 83, 4092-101. PMID: 19244326