Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583, United States; School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, United States.
Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583, United States; School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, United States.
Virology. 2018 Aug;521:158-168. doi: 10.1016/j.virol.2018.06.005. Epub 2018 Jun 21.
The V3 loop of the human immunodeficiency virus type 1 (HIV-1) gp120 exterior envelope glycoprotein (Env) becomes exposed after CD4 binding and contacts the coreceptor to mediate viral entry. Prior to CD4 engagement, a hydrophobic patch located at the tip of the V3 loop stabilizes the non-covalent association of gp120 with the Env trimer of HIV-1 subtype B strains. Here, we show that this conserved hydrophobic patch (amino acid residues 307, 309 and 317) contributes to gp120-trimer association in HIV-1 subtype C, HIV-2 and SIV. Changes that reduced the hydrophobicity of these V3 residues resulted in increased gp120 shedding and decreased Env-mediated cell-cell fusion and virus entry in the different primate immunodeficiency viruses tested. Thus, the hydrophobic patch is an evolutionarily conserved element in the tip of the gp120 V3 loop that plays an essential role in maintaining the stability of the pre-triggered Env trimer in diverse primate immunodeficiency viruses.
人类免疫缺陷病毒 1 型（HIV-1）gp120 外膜糖蛋白（Env）的 V3 环在与 CD4 结合后暴露出来，并与辅助受体接触以介导病毒进入。在与 CD4 结合之前，位于 V3 环尖端的疏水区稳定了 gp120 与 HIV-1 亚型 B 株 Env 三聚体的非共价结合。在这里，我们表明这个保守的疏水区（氨基酸残基 307、309 和 317）有助于 HIV-1 亚型 C、HIV-2 和 SIV 中的 gp120 三聚体的结合。降低这些 V3 残基疏水性的改变导致 gp120 脱落增加，以及不同灵长类免疫缺陷病毒中 Env 介导的细胞-细胞融合和病毒进入减少。因此，疏水区是 gp120 V3 环尖端的一个进化保守的元件，在维持不同灵长类免疫缺陷病毒中预触发的 Env 三聚体的稳定性方面发挥着重要作用。
