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

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub 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

{"title":"Contribution of intact viral genomes persisting in blood and tissues during ART to plasma viral rebound in SHIV-infected rhesus macaques","authors":"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","doi":"10.1016/j.isci.2025.111998","DOIUrl":null,"url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111998"},"PeriodicalIF":4.6000,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"iScience","FirstCategoryId":"103","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2589004225002585","RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

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.

Abstract Image

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

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.