Determinants of neutralization resistance in the envelope glycoproteins of a simian-human immunodeficiency virus passaged in vivo
Determinants of neutralization resistance in the envelope glycoproteins of a simian-human immunodeficiency virus passaged in vivo
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DOI：
10.1128/jvi.73.10.8873-8879.1999
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发表时间：
1999-10-01
影响因子：
5.4
通讯作者：
Sodroski, J
中科院分区：
文献类型：
--
作者：
Etemad-Moghadam, B;Sun, Y;Sodroski, J
猴-人免疫缺陷病毒（SHIV-89.6）的体内传代产生了一种病毒SHIV-89.6P，该病毒对某些中和抗体表现出增加的抗性（G. B。Karlsson等人，J. Exp. 188：1159-1171，1998）。在这里，我们研究了人类免疫缺陷病毒1型（HIV-1）中和抗体的范围，传代病毒变得耐药，并确定抗体抗性的包膜糖蛋白决定簇。与亲本SHIV-89.6的包膜糖蛋白相比，传代病毒的包膜糖蛋白对针对gp 120 V3可变环和CD 4结合位点的抗体具有抗性。相比之下，两种病毒包膜糖蛋白对分别识别gp 120和gp 41上免疫原性差的结构的两种抗体2G 12和2F 5的中和同样敏感。gp 120的V2和V3可变环中的变化对于完全抵抗IgG 1b 12抗体是必要和充分的，IgG 1b 12抗体针对CD 4结合位点。V3环中的变化指定对V3环定向抗体的完全抗性，而V1/V2环中的变化赋予对该抗体的部分抗性。中和抗体的表位未被耐药相关变化破坏。这些结果表明，在体内选择发生的HIV-1包膜糖蛋白与可变环构象，限制抗体的免疫原性中和表位的访问。
In vivo passage of a simian-human immunodeficiency virus (SHIV-89.6) generated a virus, SHIV-89.6P, that exhibited increased resistance to some neutralizing antibodies (G. B. Karlsson et al., J. Exp. Med. 188:1159-1171, 1998). Here we examine the range of human immnnodeficiency virus type 1 (HIV-1) neutralizing antibodies to which the passaged virus became resistant and identify envelope glycoprotein determinants of antibody resistance. Compared with the envelope glycoproteins derived from the parental SHIV-89.6, the envelope glycoproteins of the passaged virus were resistant to antibodies directed against the gp120 V3 variable loop and the CD4 binding site. By contrast, both viral envelope glycoproteins were equally sensitive to neutralization by two antibodies, 2G12 and 2F5, that recognize poorly immunogenic structures on gp120 and gp41, respectively. Changes in the V2 and V3 variable loops of gp120 were necessary and sufficient for full resistance to the IgG1b12 antibody, which is directed against the CD4 binding site. Changes in the V3 loop specified complete resistance to a V3 loop-directed antibody, while changes in the V1/V2 loops conferred partial resistance to this antibody. The epitopes of the neutralizing antibodies were not disrupted by the resistance-associated changes. These results indicate that in vivo selection occurs for HIV-1 envelope glycoproteins with variable loop conformations that restrict the access of antibodies to immunogenic neutralization epitopes.