Immune escape mutations selected by neutralizing antibodies in natural HIV-1 infection can alter coreceptor usage repertoire of the transmitted/founder virus.

Immune escape mutations selected by neutralizing antibodies in natural HIV-1 infection can alter coreceptor usage repertoire of the transmitted/founder virus.
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DOI:
10.1016/j.virol.2022.01.010
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发表时间:
2022-03
期刊:
影响因子:
3.7
通讯作者:
Song, Hongshuo
Song, Hongshuo
中科院分区:
医学3区
文献类型:
--
作者:
Marichannegowda, Manukumar Honnayakanahalli;Song, Hongshuo

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HIV-1在体内逃避中和抗体(NAb)的能力已得到充分证明,但除了免疫逃逸本身之外,NAb逃逸突变对HIV-1表型的影响很少被研究。在这里,我们证明体内 V3-聚糖特异性 NAb 选择的免疫逃逸突变可以改变传播/创始人 (T/F) HIV-1 的辅助受体使用库。在一名参与者产生 V3-聚糖 NAb 反应时,V3 N301 和 N332 聚糖位点的自然选择的逃逸突变废除了 CCR8 的使用,同时赋予同源 T/F 菌株 APJ 的使用。 N301 聚糖的突变也会损害 CCR3 的使用,并部分损害 CCR5 的使用效率,而 N332 聚糖位点的单个逃逸突变可以完全恢复 CCR5 的使用效率。我们的研究证明了自然 HIV-1 感染中 NAb 逃逸与辅助受体使用改变之间的联系,并表明 NAb 反应可以驱动体内病毒进入趋向性进化。
The ability of HIV-1 to evade neutralizing antibodies (NAbs) in vivo is well demonstrated, but the impact of NAb escape mutations on HIV-1 phenotype other than immune escape itself has rarely been studied. Here, we show that immune escape mutations selected by V3-glycan specific NAbs in vivo can alter coreceptor usage repertoire of the transmitted/founder (T/F) HIV-1. In a participant developed V3-glycan NAb response, naturally selected escape mutations at the V3 N301 and N332 glycan sites abrogated CCR8 usage while conferred APJ usage on the cognate T/F strain. Mutations at the N301 glycan also impaired CCR3 usage and partially compromised the efficiency in using CCR5, which could be fully restored by a single escape mutation at the N332 glycan site. Our study demonstrates the link between NAb escape and coreceptor usage alteration in natural HIV-1 infection and indicates that NAb response could drive virus entry tropism evolution in vivo.
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