Laboratory of Immunoregulation, Division of Intramural Research (DIR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
J Infect Dis. 2012 Nov;206(9):1433-42. doi: 10.1093/infdis/jis503. Epub 2012 Sep 19.
A genetic bottleneck is known to exist for human immunodeficiency virus (HIV) at the point of sexual transmission. However, the nature of this bottleneck and its effect on viral diversity over time is unclear.
Interhost and intrahost HIV diversity was analyzed in a stable population in Rakai, Uganda, from 1994 to 2002. HIV-1 envelope sequences from both individuals in initially HIV-discordant relationships in which transmission occurred later were examined using Sanger sequencing of bulk polymerase chain reaction (PCR) products (for 22 couples), clonal analysis (for 3), and next-generation deep sequencing (for 9).
Intrahost viral diversity was significantly higher than changes in interhost diversity (P < .01). The majority of HIV-1-discordant couples examined via bulk PCR (16 of 22 couples), clonal analysis (3 of 3), and next-generation deep sequencing (6 of 9) demonstrated that the viral populations present in the newly infected recipient were more closely related to the donor partner's HIV-1 variants found earlier during infection as compared to those circulating near the estimated time of transmission (P = .03).
These findings suggest that sexual transmission constrains viral diversity at the population level, partially because of the preferential transmission of ancestral as opposed to contemporary strains circulating in the transmitting partner. Future successful vaccine strategies may need to target these transmitted ancestral strains.
已知人类免疫缺陷病毒（HIV）在性传播时存在遗传瓶颈。然而，这种瓶颈的性质及其对病毒多样性随时间的影响尚不清楚。
1994 年至 2002 年，在乌干达拉凯的一个稳定人群中分析了宿主间和宿主内 HIV 多样性。使用 Sanger 测序对聚合酶链反应（PCR）产物进行批量分析（22 对夫妻）、克隆分析（3 对夫妻）和下一代深度测序（9 对夫妻），检测最初 HIV 不一致的关系中传播后发生的个体中 HIV-1 包膜序列。
宿主内病毒多样性明显高于宿主间多样性的变化（P<.01）。通过批量 PCR（22 对夫妻中的 16 对）、克隆分析（3 对夫妻中的 3 对）和下一代深度测序（9 对夫妻中的 6 对）检测到的大多数 HIV-1 不一致的夫妻，与受感染的新受体中存在的病毒种群与感染早期发现的供体伙伴的 HIV-1 变体相比，与估计的传播时间附近循环的病毒更密切相关（P=0.03）。
这些发现表明，性传播在群体水平上限制了病毒多样性，部分原因是与传播伴侣中循环的当代株相比，优先传播了祖先株。未来成功的疫苗策略可能需要针对这些传播的祖先株。
