加拿大蒙特利尔大学Nicolas Chomont团队近期取得重要工作进展,他们研究发现HIV能迅速靶向多样化的 CD4+ T细胞库以建立生产性和潜伏性感染。这一研究成果2023年2月17日在线发表于《免疫》杂志上。
据介绍,一旦感染艾滋病毒(HIV),病毒会在1-2周内传播到整个人体,然而,它的早期细胞靶点仍很难确定。
研究人员使用单细胞方法从HIV感染早期的个体中检索血液和淋巴组织中感染细胞的表型和TCR序列。HIV最初靶向少数增殖记忆CD4+ T细胞,这些细胞表面显示出高表达的CCR5。生产性感染细胞的表型因Fiebig阶段以及血液和淋巴结之间有所不同。有效感染细胞的TCR库存在严重偏差,优先感染先前扩增和传播的克隆,但几乎完全由独特的克隆型组成,表明它们是独立感染事件的产物。潜在的基因完整原病毒在感染早期就已被存档。
因此,生产性感染最初是在表型和克隆型不同的T细胞池中建立的,而潜伏感染的细胞是同时产生的。
附:英文原文
Title: HIV rapidly targets a diverse pool of CD4+ T cells to establish productive and latent infections
Author: Pierre Gantner, Supranee Buranapraditkun, Amélie Pagliuzza, Caroline Dufour, Marion Pardons, Julie L. Mitchell, Eugène Kroon, Carlo Sacdalan, Nicha Tulmethakaan, Suteeraporn Pinyakorn, Merlin L. Robb, Nittaya Phanuphak, Jintanat Ananworanich, Denise Hsu, Sandhya Vasan, Lydie Trautmann, Rémi Fromentin, Nicolas Chomont
Issue&Volume: 2023-02-17
Abstract: Upon infection, HIV disseminates throughout the human body within 1–2 weeks. However,its early cellular targets remain poorly characterized. We used a single-cell approachto retrieve the phenotype and TCR sequence of infected cells in blood and lymphoidtissue from individuals at the earliest stages of HIV infection. HIV initially targeteda few proliferating memory CD4+ T cells displaying high surface expression of CCR5. The phenotype of productivelyinfected cells differed by Fiebig stage and between blood and lymph nodes. The TCRrepertoire of productively infected cells was heavily biased, with preferential infectionof previously expanded and disseminated clones, but composed almost exclusively ofunique clonotypes, indicating that they were the product of independent infectionevents. Latent genetically intact proviruses were already archived early in infection.Hence, productive infection is initially established in a pool of phenotypically andclonotypically distinct T cells, and latently infected cells are generated simultaneously.
DOI: 10.1016/j.immuni.2023.01.030
Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00042-0
Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新IF:43.474
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