Overview
| Gender | Male |
|---|---|
| matthew.evans@mssm.edu | |
| Education and Training | Ph.D., Columbia University |
| Postdoctoral Fellowship, The Rockefeller University |
Our first goal is the identification of the host cell machinery required for viral entry. For HCV, entry is exclusively restricted to hepatocytes. This suggests that these cells express required factors not present in other cells. To identify such factors we conducted a complementation screen, where an HCV permissive cell cDNA library was screened for genes capable of rendering a nonpermissive cell HCVpp infectable. In this manner we identified Claudin-1, a component of the tight junction (TJ) required to seal off the basolateral and apical spaces of polarized epithelial cells, as an essential HCV receptor (Evans et al., Nature 2007). We are currently performing a similar screen to identify human genes able to confer HCV susceptibility to murine cells. Successful identification of such factors would be a major step towards the development of new mouse models. We also intend to carryout siRNA and small molecular screens as alternative means to identify additional the cellular machinery required for HCV entry.
The identification of CLDN1 as an essential HCV entry factor suggests that cell polarity may be an important aspect of the HCV entry process. We are utilizing polarized cell models to study HCV entry in this specialized setting. The mechanisms of this process can be probed by the addition of inhibitors specific for each entry factor to determine how they are utilized by the incoming virus. We also wish to visualize the HCV entry process by fluorescently labeling host and viral entry factors and observed their localization during infection.
