Comprehensive in vitro analysis of simian retrovirus type 4 susceptibility to antiretroviral agents
Comprehensive in vitro analysis of simian retrovirus type 4 susceptibility to antiretroviral agents
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猿猴逆转录病毒 4 型对抗逆转录病毒药物敏感性的综合体外分析
DOI：
10.1128/jvi.03208-12
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发表时间：
2013
影响因子：
5.4
通讯作者：
Matsuoka M.
中科院分区：
文献类型：
--
作者：
Tognmi;H.;Shimura;K.;Okamoio;M.;Yoshikawa;R.;MiyazHwa;T.;Matsuoka M.
猿猴逆转录病毒4型（SV-4），猿猴D型逆转录病毒，自然感染食蟹猴，通常没有明显的症状。然而，一些受感染的猴子表现出类似于猿免疫缺陷病毒感染引起的免疫抑制综合征。抗逆转录病毒药物具有抑制SRV-4的活性，被认为是有前途的药物，以打击SRV-4感染。然而，尽管已经报道了一些抗逆转录病毒药物对SRV-1和SRV-2具有抑制活性，但尚未研究具有抗SRV-4活性的抑制剂。在这项研究中，我们确定了抗逆转录病毒药物与抗-SRV-4活性的面板抗人类免疫缺陷病毒（HIV）的药物，使用robustin玻璃荧光素酶报告分析。其中，两种HIV逆转录酶抑制剂齐多夫定（AZT）和富马酸替诺福韦酯（TDF）在亚微摩尔至纳摩尔范围内有效抑制SRV-4感染，这与抗HIV-1、莫洛尼鼠白血病病毒和猫免疫缺陷病毒的活性相似或更高。相反，非核苷类逆转录酶抑制剂和蛋白酶抑制剂对SRV-4没有表现出任何活性。虽然AZT和TDF都有效地抑制了无细胞的SRV-4传播，但它们对细胞间传播仅表现出部分抑制活性。重要的是，一种HIV整合酶链转移抑制剂雷特格韦（RAL）有效抑制单轮感染以及无细胞和细胞间的SRV-4传播。这些发现表明，病毒扩增途径影响抗逆转录病毒药物对SRV-4的抑制活性，而只有RAL在抑制最初的SRV-4感染和随后的SRV-4复制方面有效。
Simian retrovirus type 4 (SRV-4), a simian type D retrovirus, naturally infects cynomolgus monkeys, usually without apparent symptoms. However, some infected monkeys presented with an immunosuppressive syndrome resembling that induced by simian immunodeficiency virus infection. Antiretrovirals with inhibitory activity against SRV-4 are considered to be promising agents to combat SRV-4 infection. However, although some antiretrovirals have been reported to have inhibitory activity against SRV-1 and SRV-2, inhibitors with anti-SRV-4 activity have not yet been studied. In this study, we identified antiretroviral agents with anti-SRV-4 activity from a panel of anti-human immunodeficiency virus (HIV) drugs using a robustin vitroluciferase reporter assay. Among these, two HIV reverse transcriptase inhibitors, zidovudine (AZT) and tenofovir disoproxil fumarate (TDF), potently inhibited SRV-4 infection within a submicromolar to nanomolar range, which was similar to or higher than the activities against HIV-1, Moloney murine leukemia virus, and feline immunodeficiency virus. In contrast, nonnucleoside reverse transcriptase inhibitors and protease inhibitors did not exhibit any activities against SRV-4. Although both AZT and TDF effectively inhibited cell-free SRV-4 transmission, they exhibited only partial inhibitory activities against cell-to-cell transmission. Importantly, one HIV integrase strand transfer inhibitor, raltegravir (RAL), potently inhibited single-round infection as well as cell-free and cell-to-cell SRV-4 transmission. These findings indicate that viral expansion routes impact the inhibitory activity of antiretrovirals against SRV-4, while only RAL is effective in suppressing both the initial SRV-4 infection and subsequent SRV-4 replication.