Cao J, Bergeron L, Helseth E, Thali M, Repke H, Sodroski J
Division of Human Retrovirology, Dana-Farber Cancer Institute, Boston, Massachusetts.
J Virol. 1993 May;67(5):2747-55. doi: 10.1128/JVI.67.5.2747-2755.1993.
Changes were introduced into conserved amino acids within the ectodomain of the human immunodeficiency virus type 1 (HIV-1) gp41 transmembrane envelope glycoprotein. The effect of these changes on the structure and function of the HIV-1 envelope glycoproteins was examined. The gp41 glycoprotein contains an amino-terminal fusion peptide (residues 512 to 527) and a disulfide loop near the middle of the extracellular domain (residues 598 to 604). Mutations affecting the hydrophobic sequences between these two regions resulted in two phenotypes. Some changes in amino acids 528 to 562 resulted in a loss of the noncovalent association between gp41 and the gp120 exterior glycoprotein. Amino acid changes in other parts of the gp41 glycoprotein (residues 608 and 628) also resulted in subunit dissociation. Some changes affecting amino acids 568 to 596 resulted in envelope glycoproteins partially or completely defective in mediating membrane fusion. Syncytium formation was more sensitive than virus entry to these changes. Changes in several amino acids from 647 to 675 resulted in higher-than-wild-type syncytium-forming ability. One of these amino acid changes affecting tryptophan 666 resulted in escape from neutralization by an anti-gp41 human monoclonal antibody, 2F5. These results contribute to an understanding of the functional regions of the HIV-1 gp41 ectodomain.
对人类免疫缺陷病毒1型（HIV-1）gp41跨膜包膜糖蛋白胞外域内的保守氨基酸进行了改变。研究了这些改变对HIV-1包膜糖蛋白结构和功能的影响。gp41糖蛋白包含一个氨基末端融合肽（第512至527位氨基酸）和靠近胞外域中部的一个二硫键环（第598至604位氨基酸）。影响这两个区域之间疏水序列的突变产生了两种表型。第528至562位氨基酸的一些变化导致gp41与gp120外部糖蛋白之间的非共价结合丧失。gp41糖蛋白其他部分（第608和628位氨基酸）的氨基酸变化也导致亚基解离。影响第568至596位氨基酸的一些变化导致包膜糖蛋白在介导膜融合方面部分或完全有缺陷。合胞体形成比病毒进入对这些变化更敏感。第647至675位几个氨基酸的变化导致形成合胞体的能力高于野生型。其中一个影响色氨酸666的氨基酸变化导致逃避抗gp41人单克隆抗体2F5的中和作用。这些结果有助于理解HIV-1 gp41胞外域的功能区域。
