A schematic representation of how HIV-1 Tat could facilitate KSHV entry into cells. (A) KSHV entry into target cells is initiated by the interaction of viral glycoproteins with binding molecules such as HSPG, followed by viral membrane fusion with KSHV-entry receptor(s) (KSHV-R). (B) HIV-1 Tat protein binds to cell-surface integrins, HSPG, and VEGFR-2. (C) Tat binds to KSHV and to cell-surface integrins HSPG and VEGFR-2, thereby concentrating KSHV on the cell surface. By bridging KSHV to the cell surface, Tat could facilitate the interaction of the virus with its entry receptor.