Deciphering Multiplicity of HIV-1C Infection: Transmission of Closely Related Multiple Viral Lineages.

Deciphering Multiplicity of HIV-1C Infection: Transmission of Closely Related Multiple Viral Lineages.
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DOI:
10.1371/journal.pone.0166746
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发表时间:
2016
期刊:
影响因子:
3.7
通讯作者:
Essex M
Essex M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Novitsky V;Moyo S;Wang R;Gaseitsiwe S;Essex M

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在大多数艾滋病毒感染中传播单一病毒变体。然而,大约20%的异性传播艾滋病毒感染是由多种病毒变异引起的。检测传播的HIV变异体并不简单,因为它涉及代表宿主内HIV-1准种的多个病毒序列的分析。我们区分两种类型的多重病毒传播的艾滋病毒感染:(1)艾滋病毒传播来自同一来源,(2)传播来自不同来源。通过单基因组扩增和测序产生了代表博茨瓦纳42名原发性HIV-1C感染者的纵向采样队列中宿主内准种的病毒序列,并跨越HIV-1C env gp 120的V1 C5区域。在每个采样时间点评估最大似然概率和成对原始距离的分布(n = 217; 42例患者;每例患者的中位数为5(IQR:4-6)个时间点,范围为每例患者2-12个时间点)。在42名个体中的9名(21%; 95 CI 10-37%)中发现了来自同一来源(可能来自已确定HIV感染的伴侣)的多种病毒变体的传播。在2例患者(5%; 95% CI 1-17%)中确定了HIV重叠感染,估计发生率为3.9/100人-年。在一个个体中观察到多种病毒的传播与稍后时间点的HIV双重感染相结合。从同一来源传播的多个HIV谱系在推断的系统发育树中产生单系分支。这样一个进化枝在HIV感染的早期阶段具有短暂的不同亚群,并遵循可预测的进化途径。随着时间的推移,最初不同的病毒谱系之间的差距逐渐填补,最初不同的亚群逐渐融合。在流行病学和人口研究中,在对艾滋病毒近度进行横断面估计时,需要考虑到对来自同一来源的多个病毒谱系传播病例的识别。
A single viral variant is transmitted in the majority of HIV infections. However, about 20% of heterosexually transmitted HIV infections are caused by multiple viral variants. Detection of transmitted HIV variants is not trivial, as it involves analysis of multiple viral sequences representing intra-host HIV-1 quasispecies. We distinguish two types of multiple virus transmission in HIV infection: (1) HIV transmission from the same source, and (2) transmission from different sources. Viral sequences representing intra-host quasispecies in a longitudinally sampled cohort of 42 individuals with primary HIV-1C infection in Botswana were generated by single-genome amplification and sequencing and spanned the V1C5 region of HIV-1C env gp120. The Maximum Likelihood phylogeny and distribution of pairwise raw distances were assessed at each sampling time point (n = 217; 42 patients; median 5 (IQR: 4–6) time points per patient, range 2–12 time points per patient). Transmission of multiple viral variants from the same source (likely from the partner with established HIV infection) was found in 9 out of 42 individuals (21%; 95 CI 10–37%). HIV super-infection was identified in 2 patients (5%; 95% CI 1–17%) with an estimated rate of 3.9 per 100 person-years. Transmission of multiple viruses combined with HIV super-infection at a later time point was observed in one individual. Multiple HIV lineages transmitted from the same source produce a monophyletic clade in the inferred phylogenetic tree. Such a clade has transiently distinct sub-clusters in the early stage of HIV infection, and follows a predictable evolutionary pathway. Over time, the gap between initially distinct viral lineages fills in and initially distinct sub-clusters converge. Identification of cases with transmission of multiple viral lineages from the same source needs to be taken into account in cross-sectional estimation of HIV recency in epidemiological and population studies.