Mutation of critical serine residues in HIV-1 matrix result in an envelope incorporation defect which can be rescued by truncation of the gp41 cytoplasmic tail.
Mutation of critical serine residues in HIV-1 matrix result in an envelope incorporation defect which can be rescued by truncation of the gp41 cytoplasmic tail.
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DOI：
10.1016/j.virol.2008.10.047
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发表时间：
2009-02-05
期刊：
影响因子：
3.7
通讯作者：
Ratner, Lee
中科院分区：
文献类型：
--
作者：
Bhatia, Ajay K.;Kaushik, Rajnish;Campbell, Nancy A.;Pontow, Suzanne E.;Ratner, Lee
人类免疫缺陷病毒1型（HIV-1）基质（MA）结构域参与病毒生命周期的早期和晚期事件。先前已经显示MA中关键丝氨酸残基的同时突变显著降低MA的磷酸化。然而，磷酸化在病毒复制中的作用仍不清楚。在位置9、67、72和77处具有丝氨酸至丙氨酸取代的病毒在其感染靶细胞的能力方面严重受损。此外，丝氨酸突变体病毒在与靶细胞膜融合的能力方面存在缺陷。有趣的是，融合缺陷和感染性缺陷都可以通过截短gp 41包膜蛋白（gp 41 CT）的长胞质尾来挽救。蔗糖密度梯度分析还揭示，与野生型病毒相比，这些突变病毒具有降低水平的整合到病毒体中的gp 120包膜蛋白。gp 41 CT的截短挽救了包膜掺入缺陷。在这里，我们提出了一个模型，在该模型中，特定的丝氨酸残基的突变，防止MA与脂筏在HIV-1组装过程中的相互作用，从而损害招聘的信封的网站病毒出芽。
The human immunodeficiency virus type 1 (HIV-1) matrix (MA) domain is involved in both early and late events of the viral life cycle. Simultaneous mutation of critical serine residues in MA has been shown previously to dramatically reduce phosphorylation of MA. However, the role of phosphorylation in viral replication remains unclear. Viruses harboring serine to alanine substitutions at positions 9, 67, 72, and 77 are severely impaired in their ability to infect target cells. In addition, the serine mutant viruses are defective in their ability to fuse with target cell membranes. Interestingly, both the fusion defect and the infectivity defect can be rescued by truncation of the long cytoplasmic tail of gp41 envelope protein (gp41CT). Sucrose density gradient analysis also reveals that these mutant viruses have reduced levels of gp120 envelope protein incorporated into the virions as compared to wild type virus. Truncation of the gp41CT rescues the envelope incorporation defect. Here we propose a model in which mutation of specific serine residues prevents MA interaction with lipid rafts during HIV-1 assembly and thereby impairs recruitment of envelope to the sites of viral budding.
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