Role of V1V2 and other human immunodeficiency virus type 1 envelope domains in resistance to neutralization during clade C infection
Role of V1V2 and other human immunodeficiency virus type 1 envelope domains in resistance to neutralization during clade C infection
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DOI：
10.1128/jvi.01839-06
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发表时间：
2007-02-01
影响因子：
5.4
通讯作者：
Derdeyn, Cynthia A.
中科院分区：
文献类型：
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作者：
Rong, Rong;Bibollet-Ruche, Frederic;Derdeyn, Cynthia A.
从赞比亚四对异性传播对的慢性（供体）和新（受体）感染伴侣中克隆并鉴定了具有生物学功能的进化枝C包膜（Env）糖蛋白。在每种情况下，供体病毒准种含有对同时期血浆自身中和有抗性的Envs，而受体Envs对供体血浆样本中的中和抗体敏感。供体Envs在gp120的V1V2高变结构域的长度、糖基化和氨基酸序列上也存在差异，而受体Envs则更为均匀。为了评估V1V2对供体Envs中和表型的贡献，将来自中和敏感受体Envs的V1V2结构域替换为供体V1V2结构域，并使用病毒假分型试验评估嵌合Envs的自身中和敏感性。长供体V1V2结构域调节对自体中和的敏感性，尽管其作用依赖于环境背景。短供体V1V2结构域不具有中和抗性。在一组受体Envs中，还发现V2的初级序列差异会影响中和敏感性。结果表明，V1V2结构域的扩展是C亚型Envs逃避自身中和的途径之一。然而，也存在与v1v2无关的耐药机制，这表明慢性C亚型感染的逃逸是多方面的。
Biologically functional clade C envelope (Env) glycoproteins from the chronically (donor) and newly (recipient) infected partners of four heterosexual transmission pairs in Zambia were cloned and characterized previously. In each case, the donor viral quasispecies contained Envs that were resistant to autologous neutralization by contemporaneous plasma, while the recipient Envs were sensitive to neutralizing antibodies in this donor plasma sample. The donor Envs also varied in length, glycosylation, and amino acid sequence of the V1V2 hypervariable domain of gp120, while the recipient Envs were much more homogeneous. To assess the contribution of V1V2 to the neutralization phenotype of the donor Envs, V1V2 domains from neutralization-sensitive recipient Envs were replaced with donor V1V2 domains, and the autologous neutralization sensitivities of the chimeric Envs were evaluated using a virus-pseudotyping assay. Long donor V1V2 domains regulated sensitivity to autologous neutralization, although the effect was dependent on the Env background. Short donor V1V2 domains did not confer neutralization resistance. Primary sequence differences in V2 were also found to influence neutralization sensitivity in one set of recipient Envs. The results demonstrate that expansion of the V1V2 domain is one pathway to escape from autologous neutralization in subtype C Envs. However, V1V2-independent mechanisms of resistance also exist, suggesting that escape is multifaceted in chronic subtype C infection.