Restricted genetic diversity of HIV-1 subtype C envelope glycoprotein from perinatally infected Zambian infants.
Restricted genetic diversity of HIV-1 subtype C envelope glycoprotein from perinatally infected Zambian infants.
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DOI：
10.1371/journal.pone.0009294
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发表时间：
2010-02-18
期刊：
影响因子：
3.7
通讯作者：
Wood C
中科院分区：
文献类型：
--
作者：
Zhang H;Tully DC;Hoffmann FG;He J;Kankasa C;Wood C
在资源有限、抗逆转录病毒治疗尚未广泛普及的地区，HIV-1 母婴传播仍然是一个重大问题。了解 HIV-1 传播过程中的最早事件并确定新传播病毒或始祖病毒的特征是干预工作的核心。在这项研究中，我们分析了 6 个母婴传播对 (MIP) 的病毒环境准种，并表征了可能影响 HIV-1 C 亚型围产期传播的包膜糖蛋白的遗传特征。从 6 个 MIP 基线样本中扩增出 env 的 V1-V5 区域，总共分析了 334 个 DNA 序列。对来自母亲和婴儿的病毒群体的比较揭示了围产期传播过程中出现的严重遗传瓶颈，其特点是婴儿中的序列多样性较低。系统发育分析表明，在我们所有的婴儿受试者中，最有可能的是单一创始人病毒造成了感染。此外，与非传播病毒相比，来自婴儿的新传播病毒在 Env V1-V5 区域中潜在的 N 连接糖基化位点明显较少，并且表现出编码较短可变环的倾向。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)。我们的研究结果表明，HIV-1 C 亚型的围产期传播过程中出现了严重的遗传瓶颈。这一点通过群体多样性和系统发育模式显而易见，其中单一病毒变体似乎导致婴儿感染。因此，新传播的病毒多样性较低，且糖基化包膜明显较少。这表明包膜糖蛋白中糖基化受到限制的病毒似乎在 HIV-1 C 亚型围产期传播期间优先传播。此外，我们的研究结果还表明，纯化选择似乎在塑造 HIV-1 C 亚型包膜序列的早期宿主进化中占主导地位。
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.
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