IN-VITRO ANTIVIRAL DRUG-SENSITIVITY OF THE KAPOSIS-SARCOMA-ASSOCIATEDHERPESVIRUS

Objective: Kaposi's sarcoma-associated herpesvirus (KSHV), or human he rpesvirus 8, has been implicated as the causative agent of Kaposi's sa rcoma. Retrospective studies show that the risk of development of Kapo si's sarcoma is significantly lower in AIDS patients who received ganc iclovir or phosphonoformic acid (PFA) therapy. Therefore, in vitro ant iviral drug sensitivity of KSHV was studied. Methods: The KSHV genome is a latent episome in lymphoma cells such as the BCBL-1 cell line. Ly tic KSHV DNA synthesis is induced by the phorbol ester 12-O-tetradecan oyl phorbol-73-acetate in BCBL-1 cells; this system was used to evalua te the effects of antiviral drugs on KSHV DNA synthesis. Results: Line ar (lytic) KSHV DNA synthesis and virus secretion was inhibited in BCB L-1 cell cultures by cidofovir (median inhibitory concentration, 0.05 mu M), ganciclovir (5.1 mu M) and PFA (97 mu M), and by aciclovir (75 mu M). Prolonged incubation of BCBL-1 cells with antiviral drugs had n o effect on episomal KSHV DNA synthesis. Conclusions: The antiviral dr ug assay developed shows that KSHV is very sensitive to cidofovir, mod erately sensitive to ganciclovir and PFA, and weakly sensitive to acic lovir. Therefore, low doses of cidofovir, or high doses of PFA or ganc iclovir could suppress clinical reactivation of KSHV. Antiviral drugs did not inhibit episomal virus DNA synthesis, suggesting that the late nt form of viral DNA is replicated by host DNA polymerases. Consequent ly, no benefit can be expected from antiviral drugs in KSHV-positive B -cell lymphomas or during latency.