Inflammatory genital infections mitigate a severe genetic bottleneck in heterosexual transmission of subtype A and C HIV-1.
Inflammatory genital infections mitigate a severe genetic bottleneck in heterosexual transmission of subtype A and C HIV-1.
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DOI：
10.1371/journal.ppat.1000274
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发表时间：
2009-01
期刊：
影响因子：
6.7
通讯作者：
Hunter, Eric
中科院分区：
文献类型：
--
作者：
Haaland, Richard E.;Hawkins, Paulina A.;Salazar-Gonzalez, Jesus;Johnson, Amber;Tichacek, Amanda;Karita, Etienne;Manigart, Olivier;Mulenga, Joseph;Keele, Brandon F.;Shaw, George M.;Hahn, Beatrice H.;Allen, Susan A.;Derdeyn, Cynthia A.;Hunter, Eric
撒哈拉以南非洲的艾滋病毒-1流行主要是由非B亚型病毒的异性传播推动的，其中C和A亚型病毒占主导地位。以前对B亚型和C亚型传播对的研究表明，来自慢性感染伴侣的单一变异可以在他们新感染的伴侣中建立感染。然而，在来自性工作者队列的A亚型感染者和来自性病诊所的B亚型个体中，感染通常是通过多种变异来确定的。这项研究检查了1750多个单基因组扩增的病毒序列，这些序列来自感染后非常早的流行病学关联的C亚型和A亚型传播对。在90%(18/20)的配对中，HIV-1感染是由来自传播伙伴准种的单一病毒变异引起的。此外，在由配偶以外的其他人感染的个人中引发感染的病毒的特征是确定生殖器感染是否缓解了在大多数流行病学相关的异性恋艾滋病毒-1传播事件中观察到的严重遗传瓶颈。在近50%(3/7)被配偶以外的其他人感染的个体中，来自单个个体的多个基因变异确定了感染。在新感染的个体中，观察到多种基因变异感染和炎性生殖器感染之间有统计学意义的相关性。因此，在绝大多数同居的异性伴侣中发生的HIV-1传播事件中，单一的基因变异确定了感染。然而，这种严重的遗传瓶颈可以通过高危伴侣中炎性生殖器感染的存在而得到缓解，这表明这种对遗传多样性的限制在很大程度上是由粘膜屏障施加的。以前关于艾滋病毒传播的研究在新感染者中确定感染的病毒的遗传异质性方面产生了相互矛盾的结果。在这项对来自赞比亚和卢旺达的被两种不同病毒基因亚型感染的人群的研究中，我们比较了新感染的个人(接受者)及其配偶(捐赠者)在感染后很早就编码了进入介导包膜糖蛋白的病毒序列，以及新感染的个人，而不是他们的配偶。尽管捐献者的病毒种群在遗传上是多样化的，但大约90%的新感染者是由单一病毒变体感染的，而其余的人是由多种病毒变体感染的。新感染的接受者体内病毒群体的同质性，以及在某些情况下，捐赠者中存在相同的病毒变体，使我们能够准确地识别传播的变体。我们能够检查每个新感染的个体的临床病史，并观察到所有被多种变异感染的个体也显示出炎症性生殖器感染的证据。我们的结果表明，生殖器粘膜对多种HIV-1基因变种的感染提供了一种天然屏障，但这种屏障可以通过炎症性生殖器感染来降低。
The HIV-1 epidemic in sub-Saharan Africa is driven largely by heterosexual transmission of non-subtype B viruses, of which subtypes C and A are predominant. Previous studies of subtype B and subtype C transmission pairs have suggested that a single variant from the chronically infected partner can establish infection in their newly infected partner. However, in subtype A infected individuals from a sex worker cohort and subtype B individuals from STD clinics, infection was frequently established by multiple variants. This study examined over 1750 single-genome amplified viral sequences derived from epidemiologically linked subtype C and subtype A transmission pairs very early after infection. In 90% (18/20) of the pairs, HIV-1 infection is initiated by a single viral variant that is derived from the quasispecies of the transmitting partner. In addition, the virus initiating infection in individuals who were infected by someone other than their spouse was characterized to determine if genital infections mitigated the severe genetic bottleneck observed in a majority of epidemiologically linked heterosexual HIV-1 transmission events. In nearly 50% (3/7) of individuals infected by someone other than their spouse, multiple genetic variants from a single individual established infection. A statistically significant association was observed between infection by multiple genetic variants and an inflammatory genital infection in the newly infected individual. Thus, in the vast majority of HIV-1 transmission events in cohabiting heterosexual couples, a single genetic variant establishes infection. Nevertheless, this severe genetic bottleneck can be mitigated by the presence of inflammatory genital infections in the at risk partner, suggesting that this restriction on genetic diversity is imposed in large part by the mucosal barrier. Previous studies of HIV transmission have yielded conflicting results regarding the genetic heterogeneity of the virus establishing infection in the newly infected individual. In this study of populations from Zambia and Rwanda that are infected by two distinct viral genetic subtypes, we compared viral sequences that encode the entry-mediating envelope glycoproteins from newly infected individuals (recipients) and their spouses (donors) very early after infection, as well as newly infected individuals infected by someone other than their spouse. In spite of the genetically diverse virus population in the donor, approximately 90% of newly infected individuals were infected by a single viral variant, while the rest were infected by multiple viral variants. The homogeneity of the virus population in the newly infected recipient, as well as the presence, in some cases, of identical virus variants in the donor, allowed us to precisely identify the transmitted variant. We were able to examine the clinical history of each newly infected individual and observed that all individuals infected by multiple variants also showed evidence of inflammatory genital infections. Our results suggest that the genital mucosa provides a natural barrier to infection by multiple genetic variants of HIV-1, but that this barrier can be lowered by inflammatory genital infections.
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