MX2 is an interferon-induced inhibitor of HIV-1 infection.
MX2 is an interferon-induced inhibitor of HIV-1 infection.
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DOI：
10.1038/nature12653
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发表时间：
2013-10-24
期刊：
影响因子：
64.8
通讯作者：
Bieniasz, Paul D.
中科院分区：
文献类型：
--
作者：
Kane, Melissa;Yadav, Shalini S.;Bitzegeio, Julia;Kutluay, Sebla B.;Zang, Trinity;Wilson, Sam J.;Schoggins, John W.;Rice, Charles M.;Yamashita, Masahiro;Hatziioannou, Theodora;Bieniasz, Paul D.
I型干扰素（IFN）可抑制HIV-1的复制，并诱导许多具有抗HIV-1活性的基因产物表达。然而，没有一种已知的抗逆转录病毒蛋白能够解释I型IFN抑制人类细胞中HIV-1复制周期的早期、整合前阶段的能力。通过比较不同细胞系中支持IFNα对HIV-1复制周期早期步骤的抑制作用的能力的基因表达谱，我们将粘病毒抗性-2（Mx2）鉴定为干扰素诱导的HIV-1感染抑制剂。Mx2的表达降低了对各种慢病毒的容许性，而使用RNA干扰去除Mx2降低了IFNα的抗HIV-1效力。HIV-1逆转录在表达Mx2的细胞中正常进行，但2-LTR环状HIV-1 DNA的丰度较低，表明Mx2抑制HIV-1核输入，或使核HIV-1 DNA不稳定。与这一观点一致，已知或怀疑改变HIV-1使用的核输入途径的HIV-1衣壳蛋白突变赋予了对Mx2的抗性，同时阻止细胞分裂增加了Mx2的效力。总体而言，这些研究结果表明，Mx2是一个效应器的抗HIV-1活性的I型IFN，并表明，Mx2抑制HIV-1感染的抑制captain依赖性核输入的亚病毒复合物。
HIV-1 replication can be inhibited by type-I interferon (IFN), and the expression of a number of gene products with anti HIV-1 activity is induced by type-I IFN. However, none of the known antiretroviral proteins can account for the ability of type-I IFN to inhibit early, preintegration, phases of the HIV-1 replication cycle in human cells. By comparing gene expression profiles in cell lines that differ in their ability to support the inhibitory action of IFNα on early steps of the HIV-1 replication cycle, we identified Myxovirus resistance-2 (Mx2) as an interferon-induced inhibitor of HIV-1 infection. Expression of Mx2 reduced permissiveness to a variety of lentiviruses, while depletion of Mx2 using RNA interference reduced the anti-HIV-1 potency of IFNα. HIV-1 reverse transcription proceeded normally in Mx2-expressing cells, but 2-LTR circular forms of HIV-1 DNA were less abundant, suggesting that Mx2 inhibits HIV-1 nuclear import, or destabilizes nuclear HIV-1 DNA. Consistent with this notion, mutations in the HIV-1 capsid protein that are known, or suspected to alter the nuclear import pathways used by HIV-1 conferred resistance to Mx2, while preventing cell division increased Mx2 potency. Overall, these findings indicate that Mx2 is an effector of the anti-HIV-1 activity of type-I IFN, and suggest that Mx2 inhibits HIV-1 infection by inhibiting capsid-dependent nuclear import of subviral complexes.
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影响因子：
64.8
作者：
Sheehy, AM;Gaddis, NC;Malim, MH
通讯作者：
Malim, MH
DOI：
10.1073/pnas.0403167101
发表时间：
2004-06-15
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影响因子：
5.4
作者：
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