Integrin alpha 3 beta 1 (CD 49c/29) Is a Cellular Receptor for Kaposi's Sarcoma-Associated Herpesvirus (KSHV/HHV-8) Entry into the Target Cells

Human herpesvirus-8 (HHV-8) is implicated in the pathogenesis of Kaposi's sarcoma. HHV-8 envelope glycoprotein B possesses the RGD motif known to interact with integrin molecules, and HHV-8 infectivity was inhibited by RGD peptides, antibodies against RGD-dependent alpha 3 and beta 1 integrins, a by soluble alpha 3 beta 1 integrin. Expression of human alpha 3 integrin increased the infectivity of virus for Chinese hamster ovary cells. Anti-gB antibodies immunoprecipitated the virus- alpha 3 and - beta 1 complexes, and virus binding studies suggest a role for alpha 3 beta 1 in HHV-8 entry. Further, HHV-8 infection induced the integrin mediated activation of focal adhesion kinase (FAK). These findings implicate a role for alpha 3 beta 1 integrin and the associated signaling pathways in HHV-8 entry into the target cells.