In vitro antiviral drug sensitivity of the Kaposi's sarcoma-associated herpesvirus.
OBJECTIVE
Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8, has been implicated as the causative agent of Kaposi's sarcoma. Retrospective studies show that the risk of development of Kaposi's sarcoma is significantly lower in AIDS patients who received ganciclovir or phosphonoformic acid (PFA) therapy. Therefore, in vitro antiviral drug sensitivity of KSHV was studied.


METHODS
The KSHV genome is a latent episome in lymphoma cells such as the BCBL-1 cell line. Lytic KSHV DNA synthesis is induced by the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate in BCBL-1 cells; this system was used to evaluate the effects of antiviral drugs on KSHV DNA synthesis.


RESULTS
Linear (lytic) KSHV DNA synthesis and virus secretion was inhibited in BCBL-1 cell cultures by cidofovir (median inhibitory concentration, 0.05 microM), ganciclovir (5.1 microM) and PFA (97 microM), and by aciclovir (75 microM). Prolonged incubation of BCBL-1 cells with antiviral drugs had no effect on episomal KSHV DNA synthesis.


CONCLUSIONS
The antiviral drug assay developed shows that KSHV is very sensitive to cidofovir, moderately sensitive to ganciclovir and PFA, and weakly sensitive to aciclovir. Therefore, low doses of cidofovir, or high doses of PFA or ganciclovir could suppress clinical reactivation of KSHV. Antiviral drugs did not inhibit episomal virus DNA synthesis, suggesting that the latent form of viral DNA is replicated by host DNA polymerases. Consequently, no benefit can be expected from antiviral drugs in KSHV-positive B-cell lymphomas or during latency.
Medveczky
M M
MM
Department of Medical Microbiology and Immunology, University of South Florida, Tampa 33612-4799, USA.
Horvath
E
E
Lund
T
T
Medveczky
P G
PG
D000212:Acyclovir / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives / Q000494:pharmacology; D004279:DNA, Viral / Q000187:drug effects / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D017245:Foscarnet / Q000494:pharmacology; D015774:Ganciclovir / Q000494:pharmacology; D019288:Herpesvirus 8, Human / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D008826:Microbial Sensitivity Tests; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D012514:Sarcoma, Kaposi / Q000188:drug therapy*; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured; D017735:Virus Latency / Q000187:drug effects
D000998:Antiviral Agents; D002273:Carcinogens; D004279:DNA, Viral; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D017245:Foscarnet; D015240:Phorbol 12,13-Dibutyrate; D003596:Cytosine; D004259:DNA-Directed DNA Polymerase; D000077404:Cidofovir; D015774:Ganciclovir; D013936:Thymidine; D000212:Acyclovir