Characterization of founder viruses in very early SIV rectal transmission.
Characterization of founder viruses in very early SIV rectal transmission.
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在非常早期的SIV直肠传播中的创始人病毒的表征。
DOI：
10.1016/j.virol.2016.12.018
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发表时间：
2017-02
期刊：
影响因子：
3.7
通讯作者：
Li Q
中科院分区：
文献类型：
--
作者：
Yuan Z;Ma F;Demers AJ;Wang D;Xu J;Lewis MG;Li Q
更好地了解HIV-1的传播对于制定预防战略至关重要。为此，我们分析了恒河猴直肠内感染后6天和10天的524个SIVmac 251全长env序列。对于大多数动物，在血浆、直肠和远端淋巴组织中没有发现创始病毒的组织区室化;然而，有一只动物存在病毒组织区室化的证据。尽管病毒接种物相同，但创始人病毒具有动物特异性，主要来源于接种物中的罕见变体，并且具有创始人病毒特征，可以区分接种物中的主要创始人变体与次要创始人或未传播变体。重要的是，传播后缺陷病毒的序列与接种物中的感受态病毒变体在遗传学上相关，并且主要通过移码而不是APOBEC介导的突变从感受态病毒变体转化而来，这表明通过移码突变将传播的病毒转化为缺陷病毒是直肠传播瓶颈的重要组成部分。
A better understanding of HIV-1 transmission is critical for developing preventative strategies. To that end, we analyzed 524 full-length env sequences of SIVmac251 at 6 and 10 days post intrarectal infection of rhesus macaques. There was no tissue compartmentalization of founder viruses across plasma, rectal and distal lymphatic tissues for most animals; however one animal has evidence of virus tissue compartmentalization. Despite identical viral inoculums, founder viruses were animal-specific, primarily derived from rare variants in the inoculum, and have a founder virus signature that can distinguish dominant founder variants from minor founder or untransmitted variants in the inoculum. Importantly, the sequences of post-transmission defective viruses were phylogenetically associated with competent viral variants in the inoculum and were mainly converted from competent viral variants by frameshift rather than APOBEC mediated mutations, suggesting the converting the transmitted viruses into defective viruses through frameshift mutation is an important component of rectal transmission bottleneck.