Vpu and Tsg101 regulate intracellular targeting of the human immunodeficiency virus type 1 core protein precursor Pr55gag
Vpu and Tsg101 regulate intracellular targeting of the human immunodeficiency virus type 1 core protein precursor Pr55gag
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DOI：
10.1128/jvi.80.8.3765-3772.2006
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发表时间：
2006-04-01
影响因子：
5.4
通讯作者：
Suomalainen, M
中科院分区：
文献类型：
--
作者：
Harila, K;Prior, I;Suomalainen, M
人类免疫缺陷病毒1型（HIV-1）的装配由病毒核心蛋白Pr 55（gag）指导。根据细胞类型，Pr 55（gag）在质膜或晚期内体/多泡体上积累。Pr 55（gag）的细胞内定位决定了病毒组装的位点，但定义Pr 55（gag）的细胞表面或内体靶向的分子机制的特征很差。我们已经分析了靶向新合成的Pr 55（gag）在HeLa H1细胞中的脉冲追踪研究和亚细胞分馏。我们的研究结果表明，Pr 55（gag）插入到质膜，当与病毒辅助蛋白Vpu共表达，Pr 55（gag）留在质膜和病毒粒子组装在这个网站。与此相反，Pr 55（gag）在Vpu的情况下表达最初插入质膜，但随后内吞，和病毒装配部分转移到内膜。这种Pr 55（gag）的内吞作用需要宿主蛋白Tsg 101。这些结果确定了一个以前未知的作用Vpu和Tsg 101作为调节器的Pr 55（gag）的内吞摄取，并建议，该网站的HIV-1大会是由调节Pr 55（gag）的内吞作用的因素。
Assembly of human immunodeficiency virus type 1 (HIV-1) is directed by the viral core protein Pr55(gag). Depending on the cell type, Pr55(gag) accumulates either at the plasma membrane or on late endosomes/ multivesicular bodies. Intracellular localization of Pr55(gag) determines the site of virus assembly, but molecular mechanisms that define cell surface or endosomal targeting of Pr55(gag) are poorly characterized. We have analyzed targeting of newly synthesized Pr55(gag) in HeLa H1 cells by pulse-chase studies and subcellular fractionations. Our results indicated that Pr55(gag) was inserted into the plasma membrane and, when coexpressed with the viral accessory protein Vpu, Pr55(gag) remained at the plasma membrane and virions assembled at this site. In contrast, Pr55(gag) expressed in the absence of Vpu was initially inserted into the plasma membrane, but subsequently endocytosed, and virus assembly was partially shifted to internal membranes. This endocytosis of Pr55(gag) required the host protein Tsg101. These results identified a previously unknown role for Vpu and Tsg101 as regulators for the endocytic uptake of Pr55(gag) and suggested that the site of HIV-1 assembly is determined by factors that regulate the endocytosis of Pr55(gag).