Identification of Interferon-Stimulated Genes with Antiretroviral Activity.

Cell host & microbe Pub Date : 2016-09-14 DOI:10.1016/j.chom.2016.08.005

Melissa Kane, Trinity M Zang, Suzannah J Rihn, Fengwen Zhang, Tonya Kueck, Mudathir Alim, John Schoggins, Charles M Rice, Sam J Wilson, Paul D Bieniasz

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Abstract

Interferons (IFNs) exert their anti-viral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). The activity of known ISGs is insufficient to account for the antiretroviral effects of IFN, suggesting that ISGs with antiretroviral activity are yet to be described. We constructed an arrayed library of ISGs from rhesus macaques and tested the ability of hundreds of individual macaque and human ISGs to inhibit early and late replication steps for 11 members of the retroviridae from various host species. These screens uncovered numerous ISGs with antiretroviral activity at both the early and late stages of virus replication. Detailed analyses of two antiretroviral ISGs indicate that indoleamine 2,3-dioxygenase 1 (IDO1) can inhibit retroviral replication by metabolite depletion while tripartite motif-56 (TRIM56) accentuates ISG induction by IFNα and inhibits the expression of late HIV-1 genes. Overall, these studies reveal numerous host proteins that mediate the antiretroviral activity of IFNs.

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具有抗逆转录病毒活性干扰素刺激基因的鉴定。

干扰素（IFNs）通过诱导数百种干扰素刺激基因（ISGs）的表达来发挥其抗病毒作用。已知isg的活性不足以解释IFN的抗逆转录病毒作用，这表明具有抗逆转录病毒活性的isg尚未被描述。我们构建了一个恒河猴isg阵列文库，并测试了数百个猕猴和人类isg个体抑制来自不同宿主物种的11种逆转录病毒科成员的早期和晚期复制步骤的能力。这些筛选发现许多isg在病毒复制的早期和晚期都具有抗逆转录病毒活性。对两种抗逆转录病毒ISG的详细分析表明，吲哚胺2,3-双加氧酶1 （IDO1）可以通过代谢物耗竭来抑制逆转录病毒的复制，而TRIM56 （tripartite motifi -56）可以增强IFNα对ISG的诱导，并抑制HIV-1晚期基因的表达。总的来说，这些研究揭示了许多介导ifn抗逆转录病毒活性的宿主蛋白。

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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Cell host & microbe

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