Sensitivity of Kaposi's sarcoma-associated herpesvirus replication to antiviral drugs - Implications for potential therapy
Sensitivity of Kaposi's sarcoma-associated herpesvirus replication to antiviral drugs - Implications for potential therapy
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DOI：
10.1172/jci119380
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发表时间：
1997-05-01
影响因子：
15.9
通讯作者：
Ganem, D
中科院分区：
文献类型：
--
作者：
Kedes, DH;Ganem, D
使用一种来源于潜伏感染卡波西肉瘤相关疱疹病毒(KSHV)的外周积液(体腔)淋巴瘤的细胞系(称为BCBL-1)，我们最近报道了在培养中成功地诱导KSHV复制(Renne，R.，W.Chung，B.Herndier，M.McGrath，N.Abbey，D.Kedes和D.Ganem)。1996年，NAT。地中海医院。2：342-346)。在这里，我们报告了第一次使用该系统来确定KSHV对现有抗病毒药物的敏感性。用佛波酯诱导潜伏感染的BCBL-1细胞裂解复制；结果表明，KSHV的复制对阿昔洛韦(9-[(2-羟乙氧基)甲基]鸟氨酸)(50%抑制浓度[IC50]=60-80mU)不敏感，但对更昔洛韦(9-[1，3-二羟基-2-丙氧甲基]鸟氨酸)(IC50=2.7-4mU)、磷甲酸钠(IC50=80-100mU)敏感。和西多福韦(1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine)(IC_(50)=0.5~1muM)。
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 mu M), but sensitive to ganciclovir (9-[1,3-dihydroxy-2-propoxymethyl]guanine) (IC50 = 2.7-4 mu M), foscarnet (trisodium phosphonoformate hexahydrate) (IC50 = 80-100 mu M), and cidofovir (1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine) (IC50 = 0.5-1 mu M).