Astrovirus Research
Human astrovirus (HAstV) infection is a major global contributor to non-bacterial gastroenteritis. However, infection by highly divergent strains of the central nervous system has also been linked to fatal neurological diseases, including encephalitis and meningitis. Of notable concern is the relatively high similarity of HAstVs with bird and other mammalian AstVs, which creates an emerging threat for zoonotic infections. Despite infection having the potential to lead to severe disease, which can be fatal, we have a poor understanding of the basics of astrovirus biology. Projects in the lab are focused on elucidating the functions of astrovirus nonstructural proteins and understanding how these proteins interact with both viral and cellular proteins to promote infection.
Flavivirus Research
Flaviviruses are positive-strand RNA viruses that replicate at the endoplasmic reticulum (ER) membrane. The virus encodes a large polyprotein that undergoes coordinated processing by both host proteases and the viral protease complex to generate equal quantities of each functional viral protein. However, not all the proteins are equally maintained in the cell. Degradation of excess individual proteins and stability of intermediate cleavage products are required for infection. This suggests that specific mechanisms involved in maintaining proper viral protein homeostasis (proteostasis) are essential for infection. However, these mechanisms are not well understood. Projects in the lab are focused on understanding how the viral protease regulates infection through temporal cleavage of the polyprotein and interactions with host proteins.
Molecular Tools Development
Dengue virus infection of U2OS cells expressing a viral protease-dependent reporter anchored to the ER. Upon viral protease cleavage of the reporter, the magenta signal translocates to the nucleus.
