鉴定具有抗逆转录病毒活性的干扰素刺激基因。
Identification of Interferon-Stimulated Genes with Antiretroviral Activity.
作者信息
Kane Melissa, Zang Trinity M, Rihn Suzannah J, Zhang Fengwen, Kueck Tonya, Alim Mudathir, Schoggins John, Rice Charles M, Wilson Sam J, Bieniasz Paul D
机构信息
Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10065, USA; Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA.
Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10065, USA; Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute, Aaron Diamond AIDS Research Center, New York, NY 10016 USA.
出版信息
Cell Host Microbe. 2016 Sep 14;20(3):392-405. doi: 10.1016/j.chom.2016.08.005.
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.
干扰素（IFNs）通过诱导数百种干扰素刺激基因（ISGs）的表达发挥其抗病毒作用。已知ISGs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ISGs尚未被描述。我们构建了一个来自恒河猴的ISGs阵列文库，并测试了数百种恒河猴和人类个体ISGs抑制来自不同宿主物种的逆转录病毒科11个成员早期和晚期复制步骤的能力。这些筛选发现了许多在病毒复制早期和晚期均具有抗逆转录病毒活性的ISGs。对两种抗逆转录病毒ISGs的详细分析表明，吲哚胺2,3-双加氧酶1（IDO1）可通过代谢物消耗抑制逆转录病毒复制，而三重模体56（TRIM56）可增强IFNα对ISG的诱导并抑制HIV-1晚期基因的表达。总体而言，这些研究揭示了众多介导IFNs抗逆转录病毒活性的宿主蛋白。
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