病毒血症
生物
抗逆转录病毒疗法
病毒学
猿猴免疫缺陷病毒
病毒载量
淋巴系统
恒河猴
人类免疫缺陷病毒(HIV)
免疫学
医学
作者
Antonio Solis-Leal,Nongthombam Boby,Suvadip Mallick,Yilun Cheng,Fei Wu,Giuliano Torre,Jason Dufour,Xavier Álvarez,Vinay Shivanna,Yaozhong Liu,Christine M. Fennessey,Jeffrey D. Lifson,Qingsheng Li,Brandon F. Keele,Binhua Ling
出处
期刊:Science Translational Medicine
[American Association for the Advancement of Science (AAAS)]
日期:2023-12-13
卷期号:15 (726)
被引量:1
标识
DOI:10.1126/scitranslmed.adi9867
摘要
The rebound-competent viral reservoir, composed of a virus that is able to persist during antiretroviral therapy (ART) and mediate reactivation of systemic viral replication and rebound viremia after ART interruption (ATI), remains the biggest obstacle to treating HIV infection. A better understanding of the cellular and tissue origins and the dynamics of viral populations that initiate rebound upon ATI could help develop therapeutic strategies for reducing the rebound-competent viral reservoir. In this study, barcoded simian immunodeficiency virus (SIV), SIVmac239M, was used to infect rhesus macaques to enable monitoring of viral barcode clonotypes contributing to virus detectable in plasma after ATI. Blood and tissues from secondary lymphoid organs (spleen, mesenteric lymph nodes, and inguinal lymph nodes) and from the colon, ileum, lung, liver, and brain were analyzed using viral barcode sequencing, intact proviral DNA assay, single-cell RNA sequencing, and combined CODEX and RNAscope in situ hybridization. Four of seven animals had viral barcodes detectable by deep sequencing of plasma at necropsy, although plasma viral RNA remained below 22 copies per milliliter. Among the tissues studied, mesenteric lymph nodes, inguinal lymph nodes, and spleen contained viral barcodes detected in plasma. CD4 + T cells were the main cell type harboring viral RNA after ATI. Furthermore, T cell zones in lymphoid tissues showed higher viral RNA abundance than B cell zones for most animals. These findings are consistent with lymphoid tissues contributing to the virus present in plasma early after ATI.
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