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Journal of Virology, December 1999, p. 10329-10338, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Human Immunodeficiency Virus Replication in a Primary Effusion Lymphoma Cell Line Stimulates Lytic-Phase Replication of Kaposi's Sarcoma-Associated Herpesvirus

Vasundhara Varthakavi,1 Philip J. Browning,2 and Paul Spearman1,*

Departments of Pediatrics and Microbiology and Immunology1 and Departments of Medicine and Cell Biology,2 Vanderbilt University, Nashville, Tennessee

Received 13 April 1999/Accepted 27 August 1999

Human immunodeficiency virus (HIV) and Kaposi's sarcoma-associated herpesvirus (KSHV) coinfect many individuals in North America and in parts of Africa. Infection with HIV is a leading risk factor for the development of Kaposi's sarcoma (KS). In this study, we tested the hypothesis that HIV infection of common or adjacent cells would stimulate replication and spread of KSHV. Infection of a primary effusion lymphoma cell line by vesicular stomatitis virus type G-pseudotyped HIV type 1 led to a rapid induction of lytic-phase KSHV replication. Induction of lytic KSHV replication by HIV required active replication of HIV. The addition of the nucleoside reverse transcriptase inhibitor azidothymidine or the protease inhibitor indinavir to the culture prevented HIV spread and inhibited the associated induction of KSHV lytic replication. Lytic replication occurred in both HIV-infected and HIV-uninfected 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 replication and was inhibited by antiretroviral drugs. These results may have implications for the pathogenesis and treatment of KS in individuals coinfected with KSHV and HIV.

* Corresponding author. Mailing address: Vanderbilt University, Pediatric Infectious Diseases, D-7235 MCN, Nashville, TN 37232-2581. Phone: (615) 322-2250. Fax: (615) 343-9723. E-mail: paul.spearman{at}mcmail.vanderbilt.edu.

Journal of Virology, December 1999, p. 10329-10338, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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