Human immunodeficiency virus replication in a primary effusion lymphoma cell line stimulates lytic-phase replication of Kaposi's sarcoma-associated herpesvirus

Human immunodeficiency virus (HIV) and Kaposi's sarcoma-associated herpesvi rus (KSHV) coinfect many individuals in North America and in parts of Afric a. Infection with HIV is a leading risk factor for the development of Kapos i's sarcoma (KS), In this study, we tested the hypothesis that HIV infectio n of common or adjacent cells would stimulate replication and spread of KSH V. Infection of a primary effusion lymphoma cell line by vesicular stomatit is virus type G-pseudotyped HIV type 1 led to a rapid induction of lytic-ph ase KSHV replication, Induction of lytic KSHV replication by HIV required a ctive replication of HIV, The addition of the nucleoside reverse transcript ase inhibitor azidothymidine or the protease inhibitor indinavir to the cul ture prevented HIV spread and inhibited the associated induction of KSHV ly tic replication. Lytic replication occurred in both HIV-infected and HIV-un infected cells within the culture, and could be induced in uninfected cells via a soluble factor released from the HIV-infected cells. Transmission of infectious KSHV to an uninfected target cell was enhanced by HIV replicati on and was inhibited by antiretroviral drugs. These results may have implic ations for the pathogenesis and treatment of KS in individuals coinfected w ith KSHV and HIV.