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首页> 外文期刊>AIDS Research and Human Retroviruses >Short communication: HIV type 1 subtype C variants transmitted through the bottleneck of breastfeeding are sensitive to new generation broadly neutralizing antibodies directed against quaternary and CD4-binding site epitopes
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Short communication: HIV type 1 subtype C variants transmitted through the bottleneck of breastfeeding are sensitive to new generation broadly neutralizing antibodies directed against quaternary and CD4-binding site epitopes

机译：简短交流：通过母乳喂养的瓶颈传播的HIV 1型C亚型变异株对针对四级和CD4结合位点表位的新一代广泛中和抗体敏感

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摘要

Mother-to-child transmission of HIV-1 subtype C can occur in utero, intrapartum, or via breast milk exposure. While not well understood, there are putative differences in the mechanisms involved with the distinct routes of vertical HIV transmission. Here, we address the question of whether specific viral characteristics are common to variants transmitted through breastfeeding that may facilitate evasion of innate or adaptive immune responses. We amplified the envelope gene (env) from the plasma of six infants during acute infection who were infected with HIV-1 subtype C through breastfeeding, and from three available matched maternal samples. We sequenced the full-length env genes in these subjects revealing heterogeneous viral populations in the mothers and homogeneous populations in the infants. In five infants, the viral population arose from a single variant, while two variants were detected in the remaining infant. Infant env sequences had fewer N-linked glycosylation sites and shorter sequences than those of the available matched maternal samples. Though the small size of the study precluded our ability to test statistical significance, these results are consistent with selection for virus with shorter variable loops and fewer glycosylation sites during transmission of HIV-1 subtype C in other settings. Transmitted envs were resistant to neutralization by antibodies 2G12 and 2F5, but were generally sensitive to the more broadly neutralizing PG9, PG16, and VRC01, indicating that this new generation of broadly neutralizing monoclonal antibodies could be efficacious in passive immunization strategies.
机译：HIV-1 C型母婴传播可发生在子宫内，产后或通过母乳暴露。尽管还没有很好地理解，但垂直HIV传播的不同途径所涉及的机制存在假定的差异。在这里，我们要解决的问题是，特定的病毒特征是否与通过母乳喂养传播的变异体共有，从而有助于逃避先天或适应性免疫应答。我们从六个通过母乳喂养感染了HIV-1亚型C的急性感染婴儿的血浆中，以及从三个匹配的母体样品中扩增了包膜基因（env）。我们对这些受试者的全长env基因进行了测序，揭示了母亲的异质病毒种群和婴儿的同质种群。在五个婴儿中，病毒种群来自一个变异株，而在其余婴儿中检测到两个变异株。婴儿env序列的N-连接糖基化位点较少，且序列比现有匹配的母体样品的序列短。尽管这项研究规模较小，但我们无法检验其统计学意义，但这些结果与选择在其他环境中传播HIV-1 C型亚型期间具有较短可变环和较少糖基化位点的病毒是一致的。传播的envs对抗体2G12和2F5的中和具有抵抗力，但通常对更广泛地中和的PG9，PG16和VRC01敏感，这表明新一代的广泛中和性单克隆抗体在被动免疫策略中可能是有效的。

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