Characteristics of IFITM, the newly identified IFN-inducible anti-HIV-1 family proteins.
Characteristics of IFITM, the newly identified IFN-inducible anti-HIV-1 family proteins.
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DOI：
10.1016/j.micinf.2012.12.003
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发表时间：
2013-04
影响因子：
5.8
通讯作者：
Suzu S
中科院分区：
文献类型：
--
作者：
Chutiwitoonchai N;Hiyoshi M;Hiyoshi-Yoshidomi Y;Hashimoto M;Tokunaga K;Suzu S
IFN诱导的IFITM蛋白（IFITM 1、2和3）通过知之甚少的机制抑制包括HIV-1在内的各种病毒的复制。在此，我们进一步分析了这些新发现的HIV-1限制因子的特征。首先，与其他抗HIV-1蛋白（如tetherin和APOBEC 3G）相比，IFITM对HIV-1蛋白的表面表达或降解的下调具有抗性。其次，IFITM的强制表达减少了用含有完整病毒序列的前病毒质粒转染的细胞中HIV-1病毒的产生。尽管与系链蛋白相比，IFITM的抑制活性是适度的，但IFITM而不是系链蛋白直接降低了包括Gag、Vif和Nef的HIV-1蛋白的表达。然而，重要的是，当这些病毒蛋白由绕过病毒特异性表达机制的密码子优化的cDNA表达时，IFITM没有抑制作用。事实上，我们的结果支持IFITM干扰由双链病毒RNA（如RRE和TAR）介导的病毒蛋白表达的想法。最后，IFITM的S-棕榈酰化对其抗流感病毒活性至关重要，但其抗HIV-1活性并不需要，这表明IFITM在不同的步骤限制这些病毒。这些特征使人们更好地理解IFITM限制HIV-1和其他病毒的机制。
IFN-inducible IFITM proteins (IFITM1, 2, and 3) inhibit the replication of various viruses including HIV-1 through poorly understood mechanisms. Here, we further analyzed characteristics of these newly identified HIV-1 restriction factors. Firstly, in contrast to other anti-HIV-1 proteins, such as tetherin and APOBEC3G, IFITMs were resistant to a down-regulation of surface expression or degradation by HIV-1 proteins. Secondly, the enforced expression of IFITMs reduced the production of HIV-1 viruses from cells transfected with proviral plasmids containing whole viral sequences. Although their inhibitory activities were modest when compared to that of tetherin, IFITMs, but not tetherin, directly reduced the expression of HIV-1 proteins including Gag, Vif and Nef. Of importance, however, IFITMs had no inhibitory effect when these viral proteins were expressed by codon-optimized cDNAs that bypassed the viral-specific expression machinery. Indeed, our results supported the idea that IFITMs interfere with viral protein expression mediated by double-stranded viral RNAs, such as RRE and TAR. Finally, the S-palmitoylation of IFITMs, which is crucial for their anti-influenza virus activity, was not required for their anti-HIV-1 activity, indicating that IFITMs restrict these viruses at different steps. These characteristics lead to a better understanding of the mechanism by which IFITMs restrict HIV-1 and other viruses.
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DOI：
10.1016/s0006-291x(03)01318-4
发表时间：
2003-08-15
影响因子：
3.1
作者：
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通讯作者：
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影响因子：
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影响因子：
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作者：
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