IFITM Proteins Restrict HIV-1 Infection by Antagonizing the Envelope Glycoprotein.
IFITM Proteins Restrict HIV-1 Infection by Antagonizing the Envelope Glycoprotein.
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DOI：
10.1016/j.celrep.2015.08.055
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发表时间：
2015-10-06
期刊：
影响因子：
8.8
通讯作者：
Liu SL
中科院分区：
文献类型：
--
作者：
Yu J;Li M;Wilkins J;Ding S;Swartz TH;Esposito AM;Zheng YM;Freed EO;Liang C;Chen BK;Liu SL
干扰素诱导的跨膜（IFITM）蛋白最近已被证明限制HIV-1和其他病毒。在这里，我们提供了IFITM蛋白，特别是IFITM 2和IFITM 3，特异性拮抗HIV-1包膜糖蛋白（Env），从而抑制病毒感染的证据。IFITM蛋白在病毒生产细胞中与HIV-1 Env相互作用，导致Env加工和病毒体掺入受损。值得注意的是，IFITM掺入HIV-1病毒体的水平与抑制程度并不严格相关。HIV-1在表达IFITM的T淋巴细胞中的延长传代导致克服IFITM限制的Env突变体的出现。IFITM抑制细胞间感染的能力可扩展至HIV-1原代分离株、HIV-2和SIV;然而，抑制程度似乎取决于病毒株。总的来说，我们的研究揭示了IFITM蛋白特异性拮抗HIV-1 Env以限制HIV-1感染的机制，并为IFITM在HIV感染中的专门作用提供了见解。IFITM抑制HIV-1细胞间感染并损害病毒感染性IFITM特异性地与HIV-1 Env相互作用并抑制Env加工IFITM掺入HIV-1病毒粒子与抑制无关IFITM对灵长类慢病毒的抑制是病毒株特异性的Yu et al.显示IFITM蛋白，特别是IFITM 2和IFITM 3，特异性拮抗HIV-1 Env糖蛋白以抑制感染。IFITM蛋白与HIV-1 Env相互作用并损害其加工和掺入病毒体。IFITM对HIV-1、HIV-2和SIV的作用具有病毒株依赖性。
The interferon-induced transmembrane (IFITM) proteins have been recently shown to restrict HIV-1 and other viruses. Here, we provide evidence that IFITM proteins, particularly IFITM2 and IFITM3, specifically antagonize the HIV-1 envelope glycoprotein (Env), thereby inhibiting viral infection. IFITM proteins interact with HIV-1 Env in viral producer cells, leading to impaired Env processing and virion incorporation. Notably, the level of IFITM incorporation into HIV-1 virions does not strictly correlate with the extent of inhibition. Prolonged passage of HIV-1 in IFITM-expressing T lymphocytes leads to emergence of Env mutants that overcome IFITM restriction. The ability of IFITMs to inhibit cell-to-cell infection can be extended to HIV-1 primary isolates, HIV-2 and SIVs; however, the extent of inhibition appears to be virus-strain dependent. Overall, our study uncovers a mechanism by which IFITM proteins specifically antagonize HIV-1 Env to restrict HIV-1 infection and provides insight into the specialized role of IFITMs in HIV infection. IFITMs inhibit HIV-1 cell-to-cell infection and impair viral infectivity IFITMs specifically interact with HIV-1 Env and inhibit Env processing IFITM incorporation into HIV-1 virions does not correlate with inhibition IFITM inhibition of primate lentiviruses is virus-strain specific Yu et al. show that IFITM proteins, particularly IFITM2 and IFITM3, specifically antagonize the HIV-1 Env glycoprotein to inhibit infection. IFITM proteins interact with HIV-1 Env and impair its processing and incorporation into virions. The effects of IFITMs on HIV-1, HIV-2, and SIVs are virus-strain dependent.