Dh. Kedes et D. Ganem, SENSITIVITY OF KAPOSIS-SARCOMA-ASSOCIATED HERPESVIRUS REPLICATION TO ANTIVIRAL DRUGS - IMPLICATIONS FOR POTENTIAL THERAPY, The Journal of clinical investigation, 99(9), 1997, pp. 2082-2086
Using a cell line (termed BCBL-1) derived from a peripheral effusion (
body cavity-based) lymphoma latently infected with Kaposi's sarcoma-as
sociated herpesvirus (KSHV), we recently reported the successful induc
tion of KSHV replication in culture (Renne, R., W. Zhong, B. Herndier,
M. McGrath, N. Abbey, D. Kedes, and D. Ganem. 1996, Nat. Med. 2:342-3
46). Here we report the first use of this system for establishing the
susceptibility of KSHV to available antiviral drugs. Latently infected
BCBL-1 cells were induced to lytic replication with phorbol esters; s
uch cells secrete large numbers of KSHV virions into the culture mediu
m, We assayed the ability of the antivirals to block KSHV production,
as measured by the release of encapsidated viral DNA, The results show
that KSHV replication is insensitive to acyclovir (9-[(2-hydroxyethox
y)-methyl]guanine) (50% inhibitory concentration [IC50] = 60-80 mu M),
but sensitive to ganciclovir (9-[1,3-dihydroxy-2-propoxymethyl]guanin
e) (IC50 = 2.7-4 mu M), foscarnet (trisodium phosphonoformate hexahydr
ate) (IC50 = 80-100 mu M), and cidofovir (S)-3-hydroxy-2-(phosphonomet
hoxy)propyl]cytosine) (IC50 = 0.5-1 mu M).