抗逆转录病毒治疗期间血液和组织中持续存在的完整病毒基因组对感染shiv的恒河猴血浆病毒反弹的贡献

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES iScience Pub Date : 2025-03-21 Epub Date: 2025-02-11 DOI:10.1016/j.isci.2025.111998

César Trifone , Corentin Richard , Amélie Pagliuzza , Caroline Dufour , Audrée Lemieux , Natasha M. Clark , Sanath K. Janaka , Christine M. Fennessey , Brandon E. Keele , Rémi Fromentin , Jacob D. Estes , Daniel E. Kaufmann , Andrés Finzi , David T. Evans , Nicolas Chomont

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引用次数: 0

摘要

持续的SIV/HIV病毒库是治疗的主要障碍，也是抗逆转录病毒治疗中断后病毒反弹的来源。然而，病毒反弹的解剖学来源仍然难以捉摸。在此，我们对5只感染shiv的恒河猴（RMs）进行抗逆转录病毒治疗28周后的血液、腹股沟、腋窝淋巴结和结肠活检中的原病毒景观进行了描述。在ati前获得的144个近全长（NFL）原病毒序列中，35%基因完整，仅2.8%存在多拷贝。ATI后血浆反弹病毒的包膜序列，与从血液或结肠中分离的序列相比，更频繁地匹配从淋巴结中提取的ATI前完整前病毒（分别有4、1和1对匹配序列）。我们的结果表明，感染细胞的克隆扩增在该模型中很少见，并且在淋巴结中持续存在的完整前病毒可能是ATI病毒反弹的优先来源。

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Contribution of intact viral genomes persisting in blood and tissues during ART to plasma viral rebound in SHIV-infected rhesus macaques

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.

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

期刊介绍： Science has many big remaining questions. To address them, we will need to work collaboratively and across disciplines. The goal of iScience is to help fuel that type of interdisciplinary thinking. iScience is a new open-access journal from Cell Press that provides a platform for original research in the life, physical, and earth sciences. The primary criterion for publication in iScience is a significant contribution to a relevant field combined with robust results and underlying methodology. The advances appearing in iScience include both fundamental and applied investigations across this interdisciplinary range of topic areas. To support transparency in scientific investigation, we are happy to consider replication studies and papers that describe negative results. We know you want your work to be published quickly and to be widely visible within your community and beyond. With the strong international reputation of Cell Press behind it, publication in iScience will help your work garner the attention and recognition it merits. Like all Cell Press journals, iScience prioritizes rapid publication. Our editorial team pays special attention to high-quality author service and to efficient, clear-cut decisions based on the information available within the manuscript. iScience taps into the expertise across Cell Press journals and selected partners to inform our editorial decisions and help publish your science in a timely and seamless way.