Trifone César, Richard Corentin, Pagliuzza Amélie, Dufour Caroline, Lemieux Audrée, Clark Natasha M, Janaka Sanath K, Fennessey Christine M, Keele Brandon E, Fromentin Rémi, Estes Jacob D, Kaufmann Daniel E, Finzi Andrés, Evans David T, Chomont Nicolas
Centre de Recherche du CHUM, Montréal, QC H2X 0A9, Canada.
Département de Microbiologie, infectiologie et immunologie, Faculté de Médecine, Université de Montréal, Montréal, QC H3T 1J4, Canada.
iScience. 2025 Feb 11;28(3):111998. doi: 10.1016/j.isci.2025.111998. eCollection 2025 Mar 21.
Persistent SIV/HIV reservoirs are the primary obstacle to a cure and the source of viral rebound after ART interruption (ATI). However, the anatomical source of viral rebound remains elusive. Here, we characterized the proviral landscape in the blood, inguinal, and axillary lymph nodes and colon biopsies of five SHIV-infected rhesus macaques (RMs), under ART for 28 weeks. From the 144 near full-length (NFL) proviral sequences obtained pre-ATI, 35% were genetically intact and only 2.8% were found in multiple copies. Envelope sequences of plasma rebounding viruses after ATI, more frequently matched pre-ATI intact proviruses retrieved from lymph nodes compared to sequences isolated from the blood or the colon (4, 1, and 1 pair of matched sequences, respectively). Our results suggest that clonal expansion of infected cells rare in this model, and that intact proviruses persisting in the lymph nodes may be a preferential source of viral rebound upon ATI.
持续存在的SIV/HIV病毒库是治愈的主要障碍以及抗逆转录病毒治疗中断（ATI）后病毒反弹的来源。然而，病毒反弹的解剖学来源仍然难以捉摸。在此，我们对五只感染SHIV的恒河猴（RMs）在接受28周抗逆转录病毒治疗期间的血液、腹股沟和腋窝淋巴结以及结肠活检组织中的前病毒格局进行了表征。从ATI前获得的144个近全长（NFL）前病毒序列中，35%在基因上是完整的，且仅有2.8%以多拷贝形式存在。与从血液或结肠中分离的序列相比，ATI后血浆中反弹病毒的包膜序列更频繁地与从淋巴结中检索到的ATI前完整前病毒相匹配（分别为4、1和1对匹配序列）。我们的结果表明，在该模型中感染细胞的克隆扩增很少见，并且在淋巴结中持续存在的完整前病毒可能是ATI后病毒反弹的优先来源。
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