Sensitivity of Kaposi's sarcoma-associated herpesvirus replication to antiviral drugs. Implications for potential therapy.

TLDR

KSHV can be induced to replicate in the BCBL‑1 cell line derived from a peripheral effusion lymphoma, enabling in‑vitro study of viral reactivation. The study aims to determine the susceptibility of KSHV replication to existing antiviral drugs. Latently infected BCBL‑1 cells were triggered into lytic replication with phorbol esters, producing abundant virions, and antiviral efficacy was assessed by measuring released encapsidated viral DNA. KSHV replication proved resistant to acyclovir (IC50 60–80 µM) but was inhibited by ganciclovir (IC50 2.7–4 µM), foscarnet (IC50 80–100 µM), and cidofovir (IC50 0.5–1 µM). Published in 1996 in *Nature Medicine*, vol.

Abstract

Using a cell line (termed BCBL-1) derived from a peripheral effusion (body cavity-based) lymphoma latently infected with Kaposi's sarcoma-associated herpesvirus (KSHV), we recently reported the successful induction of KSHV replication in culture (Renne, R., W. Zhong, B. Herndier, M. McGrath, N. Abbey, D. Kedes, and D. Ganem. 1996. Nat. Med. 2:342-346). 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; such cells secrete large numbers of KSHV virions into the culture medium. 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-hydroxyethoxy)-methyl]guanine) (50% inhibitory concentration [IC50] = 60-80 microM), but sensitive to ganciclovir (9-[1,3-dihydroxy-2-propoxymethyl]guanine) (IC50 = 2.7-4 microM), foscarnet (trisodium phosphonoformate hexahydrate) (IC50 = 80-100 microM), and cidofovir (1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine) (IC50 = 0.5-1 microM).