Molecular mechanism of virus entry into cells, virus regulation of immune response, and viral pathogenesi
Our
research interests focus on understanding the molecular mechanisms of
virus-cell interactions that lead to viral pathogenesis. At present our
focus is on virus entry into cells, the initial step in virus invasion
of a host. We utilize the human pathogen, herpes simplex virus (HSV),
as our model system.
An emerging paradigm in virus
infection of cells asserts that interaction of virus with two or more
cellular co-receptor molecules is required for virus entry into cells.
For HSV, five viral glycoproteins (gB, gC, gD, gH, and gL) and at least
two cellular components are required to mediate virus invasion of a
cell. HSV interacts through viral glycoproteins gC and/or gB with
glycosaminoglycans chains on cell surface proteoglycans to initiate
virus binding to the cell surface. Viral glycoprotein gD interaction
with the cellular coreceptor, such as herpesvirus entry mediator (HVEM)
promotes virus-cell interactions that lead to fusion of the virus
envelope with the cell membrane. Cellular interactions involving viral
glycoproteins gH and gL, essential for virus penetration into cells,
have yet to be defined.
Cellular coreceptors function
not only in virus entry, but also in virus-mediated cell-cell fusion
and potential modulation of immune response to HSV infection. Genetic
and biochemical studies of protein-protein and protein-carbohydrate
interactions are used in our laboratory to explore the molecular
mechanisms of virus entry and virus-mediated cell-cell fusion. These
are implemented by cell culture systems to define the functions
elicited by these interactions. We are also developing novel cell and
cell-free systems to define and explore the function of other viral and
cellular components necessary for virus infection.