Human immunodeficiency virus type-1 activates lytic cycle replication of Kaposi's sarcoma-associated herpesvirus through induction of KSHV Rta.

Human immunodeficiency virus type-1 (HIV-1) infection dramatically increases the risk of development of Kaposi's sarcoma (KS) in individuals infected with Kaposi's sarcoma-associated herpesvirus (KSHV). In a primary effusion lymphoma (PEL) tissue culture model system, HIV-1 replication potently induced the lytic replication of KSHV and led to the secretion of soluble factors capable of inducing lytic KSHV replication in bystander cells. Here we demonstrate that HIV induces KSHV lytic replication through activation of the KSHV Rta. HIV gene expression activated the KSHV Rta promoter following viral infection or after transfection of proviral DNA. Although HIV-1 Tat has previously been implicated as an activator of KSHV lytic replication, Tat alone was unable to activate lytic replication and failed to activate the Rta promoter. We conclude that HIV activates KSHV lytic replication by inducing the KSHV Rta promoter and that factors other than HIV-1 Tat are required to mediate this effect.