A Long Cytoplasmic Loop Governs the Sensitivity of the Anti-viral Host Protein SERINC5 to HIV-1 Nef.
A Long Cytoplasmic Loop Governs the Sensitivity of the Anti-viral Host Protein SERINC5 to HIV-1 Nef.
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DOI：
10.1016/j.celrep.2017.12.082
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发表时间：
2018-01-23
期刊：
影响因子：
8.8
通讯作者：
Göttlinger H
中科院分区：
文献类型：
--
作者：
Dai W;Usami Y;Wu Y;Göttlinger H
我们最近鉴定了多通道跨膜蛋白SERINC 5作为一种抗病毒蛋白，可以有效地抑制HIV-1感染性，并被HIV-1 Nef抵消。我们现在报告抗HIV-1活性，但不敏感Nef，是保守的脊椎动物SERINC 5蛋白。然而，Nef抗性SERINC 5在其细胞内环4（ICL 4）被Nef敏感的人SERINC 5的细胞内环4（ICL 4）取代时变得Nef敏感。相反，当人SERINC 5的ICL 4被Nef抗性SERINC 5的ICL 4取代时，人SERINC 5变得对Nef具有抗性。一般来说，当转移到敏感的SERINC时，对给定Nef表现出抗性的SERINC的ICL 4区域赋予对相同Nef的抗性，反之亦然。我们的研究结果表明，即使在Nef的存在下，人SERINC 5也可以被修饰以限制HIV-1的感染性。人SERINC 5有效抑制HIV-1感染性，但被HIV-1 Nef抵消。Dai等表明SERINC 5的细胞内环区在其对Nef的敏感性中起重要作用，并且人SERINC 5可以被修饰以抑制HIV-1，即使在Nef存在下也是如此。
We recently identified the multipass transmembrane protein SERINC5 as an antiviral protein that can potently inhibit HIV-1 infectivity and is counteracted by HIV-1 Nef. We now report that the anti-HIV-1 activity, but not the sensitivity to Nef, is conserved among vertebrate SERINC5 proteins. However, a Nef-resistant SERINC5 became Nef sensitive when its intracellular loop 4 (ICL4) was replaced by that of Nef-sensitive human SERINC5. Conversely, human SERINC5 became resistant to Nef when its ICL4 was replaced by that of a Nef-resistant SERINC5. In general, ICL4 regions from SERINCs that exhibited resistance to a given Nef conferred resistance to the same Nef when transferred to a sensitive SERINC, and vice versa. Our results establish that human SERINC5 can be modified to restrict HIV-1 infectivity even in the presence of Nef. Human SERINC5 potently inhibits HIV-1 infectivity but is counteracted by HIV-1 Nef. Dai et al. show that an intracellular loop region of SERINC5 plays an important role in its sensitivity to Nef and that human SERINC5 can be modified to inhibit HIV-1 even in the presence of Nef.
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影响因子：
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影响因子：
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