Research
Virus Entry and Host Cell Signaling
I. Vaccinia Virus Entry
Vaccinia virus (VV) is a large enveloped DNA virus and belongs to the poxvirus family. VV has a wide host range and infects different cell types in vitro and in vivo. VV enters cells by membrane fusion and no receptor was identified yet. We have demonstrated that vaccinia virus contains three envelope proteins,A27L, H3L and D8L, for binding to cell surface heparan sulfate (HS) and chondroitin sulfate (CS). Recently, we undertook a proteomic approach and determined the vaccinia virus proteome. Novel envelope proteins are identified and their roles in virus entry are currently under investigation. In addition, we have shown that vaccinia virus penetrates into cells through plasma membrane lipid rafts which act as platforms for signaling regulation. We have identified a cellular molecule that is specifically recruited to lipid rafts during virus entry and is required for virus penetration into cells. Further studies will shed light on the molecular mechanism of virus penetration, uncoating and intracellular trafficking in cells.
II. Host Restriction Mechanism Antagonized By a VV Host Range Protein CP77
Vaccinia virus growth in the restrictive CHO cells often leads to apoptosis and no virion production. In these cells, expression of a viral host range (hr) protein, CP77, is essential to rescue virus growth. Currently, we are focusing on structural and functional analyses of CP77 proteins and its cellular targets to understand how cells trigger antiviral signaling and how viral hr proteins overcome host restriction. We found that CP77 binds to 5 cellular proteins in Y2H analyses and recent results showed that one of them is called HMG20A that transiently associated with viral DNA during replication in restrictive cells. Other cellular targets are under investigation now.
