Sensitivity of Kaposi's sarcoma-associated herpesvirus replication to antiviral drugs. Implications for potential therapy.
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).
Kedes
D H
DH
Department of Microbiology and Immunology, University of California, San Francisco 94143, USA.
Ganem
D
D
D000212:Acyclovir / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives / Q000494:pharmacology; D015342:DNA Probes / Q000235:genetics; D004279:DNA, Viral / Q000097:blood; D017245:Foscarnet / Q000494:pharmacology; D015774:Ganciclovir / Q000494:pharmacology; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D019288:Herpesvirus 8, Human / Q000187:drug effects*; D006801:Humans; D008782:Methylurea Compounds / Q000494:pharmacology; D009693:Nucleic Acid Hybridization; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012514:Sarcoma, Kaposi / Q000188:drug therapy / Q000821:virology*; D014407:Tumor Cells, Cultured; D014633:Valine / Q000031:analogs & derivatives; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D015342:DNA Probes; D004279:DNA, Viral; D017320:HIV Protease Inhibitors; D008782:Methylurea Compounds; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D010703:Phorbol Esters; D011725:Pyridines; D017245:Foscarnet; D003596:Cytosine; C079555:Abbott 77003; D014633:Valine; D000077404:Cidofovir; D015774:Ganciclovir; D000212:Acyclovir