Université de Tours et CHRU de Tours, Inserm U1259, Tours.
Université Paris Sud, Université Paris Saclay, CESP Inserm U1018.
AIDS. 2018 Sep 10;32(14):1917-1926. doi: 10.1097/QAD.0000000000001906.
Transmission of HIV-1 involves a bottleneck in which generally a single HIV-1 variant from a diverse viral population in the transmitting partner establishes infection in the new host. It is still unclear to what extent this event is driven by specific properties of the transmitted viruses or the result of a stochastic process. Our study aimed to better characterize this phenomenon and define properties shared by transmitted viruses.
We compared antigenic and functional properties of envelope glycoproteins of viral variants found during primary infection in 27 patients belonging to eight transmission chains.
We generated pseudotyped viruses expressing Env variants of the viral quasispecies infecting each patient and compared their sensitivity to neutralization by eight human monoclonal broadly neutralizing antibodies (HuMoNAbs). We also compared their infectious properties by measuring their infectivity and sensitivity to various entry inhibitors.
Transmitted viruses from the same transmission chain shared many properties, including similar neutralization profiles, sensitivity to inhibitors, and infectivity, providing evidence that the transmission bottleneck is mainly nonstochastic. Transmitted viruses were CCR5-tropic, sensitive to MVC, and resistant to soluble forms of CD4, irrespective of the cluster to which they belonged. They were also sensitive to HuMoNAbs that target V3, the CD4-binding site, and the MPER region, suggesting that the loss of these epitopes may compromise their capacity to be transmitted.
Our data suggest that the transmission bottleneck is governed by selective forces. How these forces confer an advantage to the transmitted virus has yet to be determined.
HIV-1 的传播涉及一个瓶颈，在这个瓶颈中，来自传播伙伴中多样化病毒群体的通常只有一个 HIV-1 变体能够在新宿主中建立感染。目前仍不清楚这种事件在多大程度上是由传播病毒的特定性质驱动的，还是由随机过程的结果驱动的。我们的研究旨在更好地描述这一现象，并确定传播病毒所共有的特性。
我们比较了 27 名患者中 8 个传播链中初次感染期间发现的病毒变异体的抗原和功能特性。
我们生成了表达每个患者感染的病毒准种中 Env 变异体的假型病毒，并比较了它们对 8 种人源单克隆广泛中和抗体（HuMoNAbs）的敏感性。我们还通过测量它们的感染性和对各种进入抑制剂的敏感性来比较它们的感染特性。
来自同一传播链的传播病毒具有许多共同特性，包括相似的中和谱、对抑制剂的敏感性和感染性，这表明传播瓶颈主要是非随机的。传播病毒均为 CCR5 嗜性，对 MVC 敏感，对可溶性 CD4 形式具有抗性，而不论其所属簇如何。它们也对靶向 V3、CD4 结合位点和 MPER 区域的 HuMoNAbs 敏感，这表明这些表位的丧失可能会损害它们的传播能力。
我们的数据表明，传播瓶颈受选择压力的控制。这些力量如何赋予传播病毒优势还有待确定。
