CNPRC, UC Davis, One Shields Ave., Davis, CA 95616, USA.
J Virol. 2010 Jul;84(14):7083-95. doi: 10.1128/JVI.00481-10. Epub 2010 May 12.
Single-genome amplification (SGA) and sequencing of HIV-1 RNA in plasma of acutely infected humans allows the identification and enumeration of transmitted/founder viruses responsible for productive systemic infection. Use of this strategy as a means for identifying transmitted viruses suggested that intrarectal simian immunodeficiency virus (SIV) inoculation of macaques recapitulates key features of human rectal infection. However, no studies have used the SGA strategy to identify vaginally transmitted virus(es) in macaques or to determine how early SIV diversification in vaginally infected animals compares with HIV-1 in humans. We used SGA to amplify 227 partial env sequences from a SIVmac251 challenge stock and from seven rhesus macaques at the earliest plasma viral RNA-positive time point after low- and high-dose intravaginal inoculation. Sequences were analyzed phylogenetically to determine the relationship of transmitted/founder viruses within and between each animal and the challenge stock. In each animal, discrete low-diversity env sequence lineages were evident, and these coalesced phylogenetically to identical or near-identical env sequences in the challenge stock, thus confirming the validity of the SGA sequencing and modeling strategy for identifying vaginally transmitted SIV. Between 1 and 10 viruses were responsible for systemic infection, similar to humans infected by sexual contact, and the set of viruses transmitted to the seven animals studied represented the full genetic constellation of the challenge stock. These findings recapitulate many of the features of sexual HIV-1 transmission in women. Furthermore, the SIV rhesus macaque model can be used to understand the factors that influence the transmission of single versus multiple SIV variants.
对急性感染人类血浆中的 HIV-1 RNA 进行单基因组扩增（SGA）和测序，可鉴定和计数负责有效全身感染的传播/起始病毒。该策略可用于识别传播病毒，表明猴免疫缺陷病毒（SIV）经直肠接种于猕猴可再现人类直肠感染的关键特征。然而，尚无研究使用 SGA 策略来鉴定猕猴阴道传播的病毒，也无法确定阴道感染动物中 SIV 的早期多样化与人类 HIV-1 相比如何。我们使用 SGA 从 SIVmac251 挑战株和 7 只猕猴在阴道接种低剂量和高剂量后最早的血浆病毒 RNA 阳性时间点扩增了 227 个部分 env 序列。对序列进行系统发育分析，以确定每个动物内和动物之间传播/起始病毒之间的关系。在每个动物中，都有明显的离散低多样性 env 序列谱系，这些谱系在系统发育上与挑战株的相同或近乎相同的 env 序列合并，从而证实了 SGA 测序和建模策略用于鉴定阴道传播 SIV 的有效性。1 至 10 种病毒负责全身感染，类似于性接触感染的人类，传播给这 7 只动物的病毒集合代表了挑战株的完整遗传组合。这些发现再现了许多女性性传播 HIV-1 的特征。此外，恒河猴 SIV 模型可用于了解影响单一或多种 SIV 变体传播的因素。
