Areas of Interest
MECHANISMS OF NOROVIRUS AND ASTROVIRUS - HOST CELL INTERACTIONS
Diarrheal disease is the second leading cause of death in children under the age of 5 worldwide according to the World Health Organization. Among the viral agents that cause diarrhea are noroviruses and astroviruses. Both viruses package a positive-sense RNA genome into non-enveloped, icosahedral capsids, and are transmitted by the fecal-oral route. Noroviruses, members of the Caliciviridae family, are highly contagious and cause infections in all age groups. With new strains emerging regularly, human noroviruses frequently appear in the popular press where they are often called "stomach bugs" or "cruise ship virus." In addition to humans, noroviruses also infect other mammals, for example pigs, cattle and mice. Astroviruses, members of the Astroviridae family, are also highly prevalent but typically only cause disease in the very young. They are detected in many mammalian and avian species, highlighting their zoonotic potential.
However, despite the importance for public health, little is known about viruses in either family and no directed disease prevention and control strategies exist for these viruses. Even knowledge of fundamental issues such as the viral life cycle and interactions with their host is lacking. Such information however is crucial in understanding how these viruses cause disease and in developing antiviral therapies for these common agents of gastroenteritis.
We use a combination viral, molecular, immunological, biochemical, and genetic approaches in transformed or primary cell culture systems and mouse models to study the biology of murine noroviruses, human noroviruses and human astroviruses. Of particular interest to my lab are the early steps (receptor binding, entry) in the viral life cycle because they are major factors in determining species or tissue specificity, virulence and ultimately the outcome of a virus infection. In addition, we investigate mechanisms governing virus-host interactions in vitro and in vivo. Current areas of study in the lab are aimed at: i) elucidating the role of cellular metabolism during norovirus infection, ii) comparative analysis of viral and host factors for human and murine norovirus infection, iii) investigating human astrovirus infection in human intestinal organoids, iv) the interplay between enteric viruses, intestinal bacteria and the host.
Passalacqua, K.D., Lu, J., Goodfellow, I., Kolawole, A.O., Arche, J.R., Maddox, R.J., Carnahan, K.E., O'Riordan, M.X.D., Wobus, C.E. (2019) Glycolysis Is an Intrinsic Factor for Optimal Replication of a Norovirus. mBIO 10, e02175-18. Featured under “research highlights” in Nature Microbiology https://www.nature.com/articles/s41579-019-0194-5
Turula, H., Bragazzi Cunha, J., Mainou, B.A., Ramakrishnan, S.K., Wilke, C.A., Gonzalez-Hernandez, M.B., Pry, A., Fava, J., Bassis, C.M., Edelman, J., Shah, Y.M., Corthesy, B., Moore, B.B., Wobus, C.E. (2018) Natural Secretory Immunoglobulins Promote Enteric Viral Infections. Journal of Virology 92, e00826-18.
Wobus, C.E. (2018) The Dual Tropism of Noroviruses. Journal of Virology 92, e01010-17
Turula, H., Wobus, C.E. (2018) The Role of the Polymeric Immunoglobulin Receptor and Secretory Immunoglobulins during Mucosal Infection and Immunity. Viruses 10, e237
Bartnicki E., Cunha, J.B., Kolawole, A.O., Wobus, C.E. (2017) Recent advances in understanding noroviruses. F1000Res. 6: e79. doi: 10.12688/f1000research.10081.1.
Stokely, J.N., Niendorf, S., Taube, S., Hoehne, M., Young, V.B., Rogers, M.A., Wobus, C.E. (2016) Prevalence of human norovirus and Clostridium difficile coinfections in adult hospitalized patients. Clinical Epidemiology 8: 253-60.
Bragazzi Cunha J., Wobus,C.E. (2016) Select membrane proteins modulate MNV-1 infection of macrophages and dendritic cells in a cell type-specific manner. Virus Research 222: 64-70.
Baldridge, M.T., Turula, H., Wobus, C.E. (2016) Norovirus Regulation by Host and Microbe. Trends in Molecular Medicine 22: 1047-1059. Review.
Kolawole, A.O., Rocha-Pereira, J., Elftman, M.D., Neyts, J., Wobus, C.E. (2016) Inhibition of human norovirus by a viral polymerase inhibitor in the B cell culture system and in the mouse model. Antiviral Research 132: 46-9.
Passalacqua, K.D., Charbonneau, M.E., Donato, N.J., Showalter, H.D., Sun, D., Wen, B., He, M., Sun, H., O'Riordan, M.X., Wobus, C.E. (2016) Anti-infective activity of 2-cyano-3-acrylamide inhibitors with improved drug-like properties against two intracellular pathogens. Antimicrobial Agents and Chemotherapy 60: 4183-96.