ASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction.
ASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction.
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DOI：
10.1038/ncomms7945
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发表时间：
2015-04-22
影响因子：
16.6
通讯作者：
Ryo, Akihide
中科院分区：
文献类型：
--
作者：
Miyakawa, Kei;Matsunaga, Satoko;Kanou, Kazuhiko;Matsuzawa, Atsushi;Morishita, Ryo;Kudoh, Ayumi;Shindo, Keisuke;Yokoyama, Masaru;Sato, Hironori;Kimura, Hirokazu;Tamura, Tomohiko;Yamamoto, Naoki;Ichijo, Hidenori;Takaori-Kondo, Akifumi;Ryo, Akihide
APOBEC3G(A3G)是一种先天的抗病毒限制因子，能强烈抑制人类免疫缺陷病毒1型(HIV-1)的复制。HIV-1辅助蛋白Vif劫持宿主泛素-蛋白酶体系统以执行3G降解。识别阻止Vif作用的宿主途径可能为阻断病毒复制提供新的策略。我们在这里证明了宿主蛋白ASK1(凋亡信号调节蛋白1)干扰了Vif的抵消作用，并重振了3G介导的病毒限制。ASK1与Vif的BC-box结合，从而破坏Vif-泛素连接酶复合体的组装。因此，ASK1稳定A3G并促进其融入病毒颗粒，最终降低病毒的传染性。此外，抗逆转录病毒药物AZT(齐多夫定)在HIV-1感染细胞中诱导ASK1表达并恢复A3G的抗病毒活性。因此，这项研究证明了ASK1在恢复宿主抗病毒系统方面的独特功能，该功能可以通过AZT治疗而增强。人类蛋白APOBEC3G(A3G)抑制HIV-1复制，但病毒蛋白Vif通过诱导A3G降解来抵消。在这里，宫川等人。结果表明，抗逆转录病毒药物AZT通过刺激宿主蛋白ASK1的表达来恢复A3G的功能，而宿主蛋白ASK1干扰了VIF的作用。
APOBEC3G (A3G) is an innate antiviral restriction factor that strongly inhibits the replication of human immunodeficiency virus type 1 (HIV-1). An HIV-1 accessory protein, Vif, hijacks the host ubiquitin–proteasome system to execute A3G degradation. Identification of the host pathways that obstruct the action of Vif could provide a new strategy for blocking viral replication. We demonstrate here that the host protein ASK1 (apoptosis signal-regulating kinase 1) interferes with the counteraction by Vif and revitalizes A3G-mediated viral restriction. ASK1 binds the BC-box of Vif, thereby disrupting the assembly of the Vif–ubiquitin ligase complex. Consequently, ASK1 stabilizes A3G and promotes its incorporation into viral particles, ultimately reducing viral infectivity. Furthermore, treatment with the antiretroviral drug AZT (zidovudine) induces ASK1 expression and restores the antiviral activity of A3G in HIV-1-infected cells. This study thus demonstrates a distinct function of ASK1 in restoring the host antiviral system that can be enhanced by AZT treatment. The human protein APOBEC3G (A3G) inhibits HIV-1 replication, but the viral protein Vif counteracts by inducing A3G degradation. Here Miyakawa et al. show that the antiretroviral drug AZT restores A3G function in vitro by stimulating expression of a host protein, ASK1, which interferes with the action of Vif.
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通讯作者：
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