Basmaciogullari Stéphane, Babcock Gregory J, Van Ryk Donald, Wojtowicz Woj, Sodroski Joseph
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
J Virol. 2002 Nov;76(21):10791-800. doi: 10.1128/jvi.76.21.10791-10800.2002.
CD4 and the chemokine receptors, CXCR4 and CCR5, serve as receptors for human immunodeficiency virus type 1 (HIV-1). Binding of the HIV-1 gp120 envelope glycoprotein to the chemokine receptors normally requires prior interaction with CD4. Mapping the determinants on gp120 for the low-affinity interaction with CXCR4 has been difficult due to the nonspecific binding of this viral glycoprotein to cell surfaces. Here we examine the binding of a panel of gp120 mutants to paramagnetic proteoliposomes displaying CXCR4 on their surfaces. We show that the gp120 beta19 strand and third variable (V3) loop contain residues important for CXCR4 interaction. Basic residues from both elements, as well as a conserved hydrophobic residue at the V3 tip, contribute to CXCR4 binding. Removal of the gp120 V1/V2 variable loops allows the envelope glycoprotein to bind CXCR4 in a CD4-independent manner. These results indicate that although some variable gp120 residues contribute to the specific binding to CCR5 or CXCR4, gp120 elements common to CXCR4- or CCR5-using strains are involved in the interaction with both coreceptors.
CD4以及趋化因子受体CXCR4和CCR5作为1型人类免疫缺陷病毒（HIV-1）的受体。HIV-1的gp120包膜糖蛋白与趋化因子受体的结合通常需要先与CD4相互作用。由于这种病毒糖蛋白与细胞表面的非特异性结合，确定gp120上与CXCR4低亲和力相互作用的决定簇一直很困难。在这里，我们研究了一组gp120突变体与表面展示CXCR4的顺磁性蛋白脂质体的结合情况。我们发现，gp120的β19链和第三个可变区（V3）环包含对CXCR4相互作用很重要的残基。这两个元件的碱性残基以及V3末端的一个保守疏水残基都有助于与CXCR4的结合。去除gp120的V1/V2可变环可使包膜糖蛋白以不依赖CD4的方式与CXCR4结合。这些结果表明，虽然gp120的一些可变残基有助于与CCR5或CXCR4的特异性结合，但使用CXCR4或CCR5的毒株共有的gp120元件参与了与这两种共受体的相互作用。
