Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding
Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding
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DOI：
10.1016/s0092-8674(01)00506-2
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发表时间：
2001-10-05
期刊：
影响因子：
64.5
通讯作者：
Sundquist, WI
中科院分区：
文献类型：
--
作者：
Garrus, JE;von Schwedler, UK;Sundquist, WI
像其他包膜病毒一样，HIV-1利用细胞机制从感染细胞中出芽。我们现在表明，Tsg 101蛋白，其功能在液泡蛋白分选（Vps），是所需的HIV-1出芽。Tsg 101的UEV结构域与结构性Gag蛋白的p6结构域内的必需四肽（PTAP）基序结合，也与遍在蛋白结合。通过小干扰RNA消耗细胞Tsg 101，在晚期阶段阻止HIV-1出芽，并且通过重新引入Tsg 101来拯救出芽。抑制空泡蛋白分选的显性负突变Vps 4蛋白也阻止HIV-1和MLV出芽。这些观察结果表明，逆转录病毒通过占用Vps途径中通常使用的细胞机器来形成多泡体而出芽。
Like other enveloped viruses, HIV-1 uses cellular machinery to bud from infected cells. We now show that Tsg101 protein, which functions in vacuolar protein sorting (Vps), is required for HIV-1 budding. The UEV domain of Tsg101 binds to an essential tetrapeptide (PTAP) motif within the p6 domain of the structural Gag protein and also to ubiquitin. Depletion of cellular Tsg101 by small interfering RNA arrests HIV-1 budding at a late stage, and budding is rescued by reintroduction of Tsg101. Dominant negative mutant Vps4 proteins that inhibit vacuolar protein sorting also arrest HIV-1 and MLV budding. These observations suggest that retroviruses bud by appropriating cellular machinery normally used in the Vps pathway to form multivesicular bodies.