AEGiS-11IAC: Drugs that inhibit herpes virus DNA synthesis block in vitro activation of the Kaposi's sarcoma-associated herpes virus in pheripheral blood mononuclear cells.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Drugs that inhibit herpes virus DNA synthesis block in vitro activation of the Kaposi's sarcoma-associated herpes virus in pheripheral blood mononuclear cells.

Int Conf AIDS 1996 Jul 7-12; 11:19 (abstract no. Th.A.928)
Shankar P, Serulneck TM, Dezube BJ, Lieberman J; The Center for Blood Research, Boston, MA. Fax: (617) 278-3493. E-mail: lieberman@cbr.med.harvard.edu.

OBJECTIVE: To determine whether lytic infection of peripheral blood mononuclear cells (PBMC) with the newly described herpesvirus (KSHV) can be blocked by drugs that inhibit herpesvirus DNA polymerase.

METHODS: RNA and DNA were isolated from the PBMC of 5 HIV-infected patients with Kaposi's sarcoma either before or after culture, in the presence or absence of phorbol ester. RNA was reverse transcribed and the cDNA and DNA were PCR-amplified and probed for sequences of the minor capsid protein of KSHV.

RESULTS: In freshly isolated PBMC from HIV-infected patients with KS, we have detected KSHV DNA, using in situ lysis agarose gel electrophoresis (Decker et al, in press), with mobilities characteristic of both latent infection (episomal DNA) as well as linear DNA associated with ongoing virion production. In this study, PBMC from 4 of 5 KS patients contained detectable KSHV sequences. Viral production, assayed by PCR amplification of KSHV minor capsid protein cDNA and DNA, was induced from the positive samples by in vitro culture of PBMC in the presence or absence of phorbol esters. Phorbol esters enhanced viral production somewhat (less than 2-fold) but were not required for in vitro KSHV activation from PBMC. Viral production was inhibited to varying degrees by each of 4 drugs (acyclovir, ganciclovir, foscavir or cidofovir) that block herpesvirus DNA replication at concentrations comparable to peak levels following iv administration.

CONCLUSIONS: KSHV production can be induced from circulating mononuclear cells of KS patients and is inhibited by antiherpes drugs in vitro. However, more detailed studies are required to determine which drugs are most effective in vitro and least likely to generate drug-resistance. The effectiveness of anti-herpesvirus drugs in the treatment or prophylaxis of KSHV-related disease needs to be evaluated.

Keywords: AEGIS, Sarcoma, Kaposi, Herpesvirus 8, Human, Virus Activation, Herpesviridae Infections, Herpesviridae, Satellite Viruses, Foscarnet, Opportunistic Infections, Ganciclovir, DNA-Directed DNA Polymerase, Acyclovir, AIDS-Related Opportunistic Infections, In Vitro, Human, virology, ICA11

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ThA928