Leyre Louise, Kroon Eugène, Vandergeeten Claire, Sacdalan Carlo, Colby Donn J, Buranapraditkun Supranee, Schuetz Alexandra, Chomchey Nitiya, de Souza Mark, Bakeman Wendy, Fromentin Rémi, Pinyakorn Suteeraporn, Akapirat Siriwat, Trichavaroj Rapee, Chottanapund Suthat, Manasnayakorn Sopark, Rerknimitr Rungsun, Wattanaboonyoungcharoen Phandee, Kim Jerome H, Tovanabutra Sodsai, Schacker Timothy W, O'Connell Robert, Valcour Victor G, Phanuphak Praphan, Robb Merlin L, Michael Nelson, Trautmann Lydie, Phanuphak Nittaya, Ananworanich Jintanat, Chomont Nicolas
Centre de Recherche du CHUM and Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montréal, QC H2X 0A9, Canada.
SEARCH, Thai Red Cross AIDS Research Centre, Bangkok 10330, Thailand.
Sci Transl Med. 2020 Mar 4;12(533). doi: 10.1126/scitranslmed.aav3491.
The timing and location of the establishment of the viral reservoir during acute HIV infection remain unclear. Using longitudinal blood and tissue samples obtained from HIV-infected individuals at the earliest stage of infection, we demonstrate that frequencies of infected cells reach maximal values in gut-associated lymphoid tissue and lymph nodes as early as Fiebig stage II, before seroconversion. Both tissues displayed higher frequencies of infected cells than blood until Fiebig stage III, after which infected cells were equally distributed in all compartments examined. Initiation of antiretroviral therapy (ART) at Fiebig stages I to III led to a profound decrease in the frequency of infected cells to nearly undetectable level in all compartments. The rare infected cells that persisted were preferentially found in the lymphoid tissues. Initiation of ART at later stages (Fiebig stages IV/V and chronic infection) induced only a modest reduction in the frequency of infected cells. Quantification of HIV DNA in memory CD4 T cell subsets confirmed the unstable nature of most of the infected cells at Fiebig stages I to III and the emergence of persistently infected cells during the transition to Fiebig stage IV. Our results indicate that although a large pool of cells is infected during acute HIV infection, most of these early targets are rapidly cleared upon ART initiation. Therefore, infected cells present after peak viremia have a greater ability to persist.
急性HIV感染期间病毒储存库建立的时间和位置仍不清楚。利用从处于感染最早阶段的HIV感染者身上获取的纵向血液和组织样本，我们证明，早在血清转化前的Fiebig II期，肠道相关淋巴组织和淋巴结中受感染细胞的频率就达到了最大值。在Fiebig III期之前，这两种组织中受感染细胞的频率均高于血液，之后受感染细胞在所有检测的区室中均匀分布。在Fiebig I至III期开始抗逆转录病毒疗法（ART）导致所有区室中受感染细胞的频率大幅下降至几乎检测不到的水平。持续存在的罕见受感染细胞优先在淋巴组织中发现。在后期阶段（Fiebig IV/V期和慢性感染）开始ART仅导致受感染细胞频率适度降低。对记忆性CD4 T细胞亚群中HIV DNA的定量分析证实，在Fiebig I至III期大多数受感染细胞的性质不稳定，并且在向Fiebig IV期转变过程中出现了持续受感染的细胞。我们的结果表明，尽管在急性HIV感染期间有大量细胞被感染，但这些早期靶点中的大多数在开始ART后会迅速清除。因此，病毒血症峰值后出现的受感染细胞具有更强的持续存在能力。
