ASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction.

IF 15.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Nature Communications Pub Date : 2015-04-22 DOI:10.1038/ncomms7945

Kei Miyakawa, Satoko Matsunaga, Kazuhiko Kanou, Atsushi Matsuzawa, Ryo Morishita, Ayumi Kudoh, Keisuke Shindo, Masaru Yokoyama, Hironori Sato, Hirokazu Kimura, Tomohiko Tamura, Naoki Yamamoto, Hidenori Ichijo, Akifumi Takaori-Kondo, Akihide Ryo

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引用次数: 31

Abstract

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.

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ASK1通过破坏HIV-1 vif介导的反作用恢复APOBEC3G的抗病毒活性。

APOBEC3G (A3G)是一种先天抗病毒限制因子，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，执行A3G降解。鉴定阻断Vif作用的宿主途径可以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(凋亡信号调节激酶1)干扰Vif的反作用，并恢复a3g介导的病毒限制。ASK1结合Vif的BC-box，从而破坏Vif泛素连接酶复合物的组装。因此，ASK1稳定了A3G并促进其与病毒颗粒的结合，最终降低了病毒的传染性。此外，用抗逆转录病毒药物AZT(齐多夫定)治疗可诱导ASK1表达并恢复hiv -1感染细胞中A3G的抗病毒活性。因此，这项研究表明ASK1在恢复宿主抗病毒系统方面具有独特的功能，AZT治疗可以增强这种功能。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.