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.