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.
Kolawole, A.O., Wobus, C.E.: Gastrointestinal organoid technology advances studies of enteric virus biology. (2020) PLoS Pathogens 16 (1): e1008212.
Graziano, V.R., Walker, F.C., Kennedy, E.A., Wei, J., Ettayebi, K., Strine, M.S., Filler, R.B., Hassan, E., Hsieh, L.L., Kim, A.S., Kolawole, A.O., Wobus, C.E., Lindesmith, L.C., Baric, R.S., Estes, M.K., Orchard, R.C., Baldridge, M.T., Wilen, C.B. (2020) CD300lf is the primary physiologic receptor of murine norovirus but not human norovirus. PLoS Pathogens 16 (4): e1008242.
Rockey, N., Young, S., Kohn, T., Pecson, B., Wobus, C.E., Raskin, L., Wigginton, K.R. (2020) UV Disinfection of Human Norovirus: Evaluating Infectivity Using a Genome-Wide PCR-Based Approach. Environmental Science and Technology 54 (5): 2851-2858.
Grau, K.R., Zhu, S., Peterson, S.T., Helm, E.W., Philip, D., Phillips, M., Hernandez, A., Turula, H., Frasse, P., Graziano, V.R., Wilen, C.B., Wobus, C.E., Baldridge, M.T., Karst, S.M. (2020) The intestinal regionalization of acute norovirus infection is regulated by the microbiota via bile acid-mediated priming of type III interferon. Nature Microbiology 5 (1): 84-92.
Kolawole, A.O., Mirabelli, C., Hill, D.R., Svoboda, S.A., Janowski, A.B., Passalacqua, K.D., Rodriguez, B.N., Dame, M.K., Freiden, P., Berger, R.P., Vu, D.L., Hosmillo, M., O'Riordan, M.X.D., Schultz-Cherry, S., Guix, S., Spence, J.R., Wang, D., Wobus,C.E. (2019) Astrovirus replication in human intestinal enteroids reveals multi-cellular tropism and an intricate host innate immune landscape. PLoS Pathogens 15 (10): e1008057.
Passalacqua, K.D., Purdy, J.G., Wobus, C.E. (2019) The inert meets the living: The expanding view of metabolic alterations during viral pathogenesis. PLoS Pathogens 15 (7): e1007830.
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.
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.