Nebraska Center for Virology, University of Nebraska, Lincoln, Nebraska, United States of America.
PLoS One. 2010 Feb 18;5(2):e9294. doi: 10.1371/journal.pone.0009294.
Mother-to-child transmission of HIV-1 remains a significant problem in the resource-constrained settings where anti-retroviral therapy is still not widely available. Understanding the earliest events during HIV-1 transmission and characterizing the newly transmitted or founder virus is central to intervention efforts. In this study, we analyzed the viral env quasispecies of six mother-infant transmission pairs (MIPs) and characterized the genetic features of envelope glycoprotein that could influence HIV-1 subtype C perinatal transmission.
The V1-V5 region of env was amplified from 6 MIPs baseline samples and 334 DNA sequences in total were analyzed. A comparison of the viral population derived from the mother and infant revealed a severe genetic bottleneck occurring during perinatal transmission, which was characterized by low sequence diversity in the infant. Phylogenetic analysis indicates that most likely in all our infant subjects a single founder virus was responsible for establishing infection. Furthermore, the newly transmitted viruses from the infant had significantly fewer potential N-linked glycosylation sites in Env V1-V5 region and showed a propensity to encode shorter variable loops compared to the nontransmitted viruses. In addition, a similar intensity of selection was seen between mothers and infants with a higher rate of synonymous (dS) compared to nonsynonymous (dN) substitutions evident (dN/dS<1).
Our results indicate that a strong genetic bottleneck occurs during perinatal transmission of HIV-1 subtype C. This is evident through population diversity and phylogenetic patterns where a single viral variant appears to be responsible for infection in the infants. As a result the newly transmitted viruses are less diverse and harbored significantly less glycosylated envelope. This suggests that viruses with the restricted glycosylation in envelope glycoprotein appeared to be preferentially transmitted during HIV-1 subtype C perinatal transmission. In addition, our findings also indicated that purifying selection appears to predominate in shaping the early intrahost evolution of HIV-1 subtype C envelope sequences.
在资源有限的环境中，抗逆转录病毒疗法仍未广泛普及，艾滋病毒 1 型母婴传播仍然是一个重大问题。了解艾滋病毒 1 型传播过程中的最早事件，并对新传播或创始病毒进行特征描述，对于干预措施至关重要。在这项研究中，我们分析了 6 对母婴传播对（MIP）的病毒 env 准种，并描述了可能影响艾滋病毒 1 型 C 亚型围产期传播的包膜糖蛋白的遗传特征。
从 6 个 MIP 基线样本中扩增 env 的 V1-V5 区，共分析了 334 个 DNA 序列。对来自母亲和婴儿的病毒群体进行比较发现，围产期传播过程中存在严重的遗传瓶颈，婴儿的序列多样性较低。系统发育分析表明，在我们所有的婴儿研究对象中，很可能只有一个创始病毒负责建立感染。此外，与未传播的病毒相比，来自婴儿的新传播病毒在 Env V1-V5 区具有显著较少的潜在 N-连接糖基化位点，并且表现出编码较短可变环的趋势。此外，母亲和婴儿之间的选择强度相似，同义（dS）替换率明显高于非同义（dN）替换率（dN/dS<1）。
我们的结果表明，艾滋病毒 1 型 C 亚型的围产期传播过程中存在强烈的遗传瓶颈。这通过群体多样性和系统发育模式得到证明，其中单一病毒变体似乎负责婴儿的感染。因此，新传播的病毒多样性较低，包膜中糖基化程度显著降低。这表明，包膜糖蛋白中受限制的糖基化病毒在艾滋病毒 1 型 C 亚型围产期传播中似乎更优先传播。此外，我们的研究结果还表明，在塑造艾滋病毒 1 型 C 亚型包膜序列的早期宿主内进化过程中，纯化选择似乎占主导地位。
