Nef proteins from simian immunodeficiency viruses are tetherin antagonists.

Nef proteins from simian immunodeficiency viruses are tetherin antagonists.
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DOI:
10.1016/j.chom.2009.05.008
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发表时间:
2009-07-23
影响因子:
30.3
通讯作者:
Hatziioannou T
Hatziioannou T
中科院分区:
医学1区
文献类型:
--
作者:
Zhang F;Wilson SJ;Landford WC;Virgen B;Gregory D;Johnson MC;Munch J;Kirchhoff F;Bieniasz PD;Hatziioannou T

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tetherin/BST2/CD317 蛋白通过诱导新生颗粒束缚到受感染的细胞表面来阻止 HIV-1 和其他包膜病毒的释放。 HIV-1 Vpu 蛋白可拮抗人类而非猴系链蛋白的抗病毒活性,并且许多猿猴免疫缺陷病毒 (SIV) 不编码 Vpu。在这里,我们发现 SIV 中明显“缺失”的抗系绳蛋白活性已被几种 SIV Nef 蛋白获得。具体而言,SIVMAC/SIVSMM、SIVAGM 和 SIVBLU Nef 蛋白可以抑制系链蛋白活性。值得注意的是,SIV Nef 蛋白的系链蛋白拮抗作用是物种特异性的,在遗传上与其他 Nef 活性是分开的,并且对于猿猴而不是人类系链蛋白最为明显。因此,系链蛋白细胞质尾部对 SIVMAC Nef 敏感性的关键决定因素在非人灵长类动物系链蛋白中是可变的,并且在人系链蛋白中被删除,这可能是由于病毒拮抗剂(可能包括 Nef 蛋白)施加的选择性压力。
The tetherin/BST2/CD317 protein blocks the release of HIV-1 and other enveloped viruses by inducing tethering of nascent particles to infected cell surfaces. The HIV-1 Vpu protein antagonizes the antiviral activity of human but not monkey tetherins and many simian immunodeficiency viruses (SIVs) do not encode Vpu. Here, we show that the apparently ‘missing’ anti-tetherin activity in SIVs has been acquired by several SIV Nef proteins. Specifically, SIVMAC/SIVSMM, SIVAGM and SIVBLU Nef proteins can suppress tetherin activity. Notably, tetherin antagonism by SIV Nef proteins is species-specific, is genetically separable from other Nef activities and is most evident with simian rather than human tetherin proteins. Accordingly, a critical determinant of sensitivity to SIVMAC Nef in the tetherin cytoplasmic tail is variable in nonhuman primate tetherins and deleted in human tetherin, likely due to selective pressures imposed by viral antagonists, perhaps including Nef proteins.
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影响因子: 5.4
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