Aberrant DNA methylation of genes regulating CD4+ T cell HIV-1 reservoir in women with HIV

IF 7.9 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Clinical and Translational Medicine Pub Date : 2025-03-11 DOI:10.1002/ctm2.70267

Ke Xu, Xinyu Zhang, Kesava Asam, Bryan C. Quach, Grier P. Page, Deborah Konkle-Parker, Claudia Martinez, Cecile D. Lahiri, Elizabeth F. Topper, Mardge H. Cohen, Seble G. Kassaye, Jack DeHovitz, Mark H. Kuniholm, Nancie M. Archin, Amir Valizadeh, Phyllis C. Tien, Vincent C. Marconi, Dana B. Hancock, Eric O. Johnson, Bradley E. Aouizerat

{"title":"Aberrant DNA methylation of genes regulating CD4+ T cell HIV-1 reservoir in women with HIV","authors":"Ke Xu, Xinyu Zhang, Kesava Asam, Bryan C. Quach, Grier P. Page, Deborah Konkle-Parker, Claudia Martinez, Cecile D. Lahiri, Elizabeth F. Topper, Mardge H. Cohen, Seble G. Kassaye, Jack DeHovitz, Mark H. Kuniholm, Nancie M. Archin, Amir Valizadeh, Phyllis C. Tien, Vincent C. Marconi, Dana B. Hancock, Eric O. Johnson, Bradley E. Aouizerat","doi":"10.1002/ctm2.70267","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>The HIV-1 reservoir in CD4+ T cells (HR<sub>CD4</sub>) pose a major challenge to curing HIV, with many of its mechanisms still unclear. HIV-1 DNA integration and immune responses may alter the host's epigenetic landscape, potentially silencing HIV-1 replication.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>This study used bisulphite capture DNA methylation sequencing in CD4+ T cells from the blood of 427 virally suppressed women with HIV to identify differentially methylated sites and regions associated with HR<sub>CD4</sub>.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>The average total HR<sub>CD4</sub> size was 1409 copies per million cells, with most proviruses defective and only a small proportion intact. The study identified 245 differentially methylated CpG sites and 85 regions linked to HR<sub>CD4</sub> size, with 52% of significant sites in intronic regions. Genes associated with HR<sub>CD4</sub> were involved in viral replication, HIV-1 latency and cell growth and apoptosis. HR<sub>CD4</sub> size was inversely related to DNA methylation of interferon signalling genes and positively associated with methylation at known HIV-1 integration sites. HR<sub>CD4</sub>-associated genes were enriched on the pathways related to immune defence, transcription repression and host–virus interactions.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>These findings suggest that HIV-1 reservoir is linked to aberrant DNA methylation in CD4+ T cells, offering new insights into epigenetic mechanisms of HIV-1 latency and potential molecular targets for eradication strategies.</p>\n </section>\n \n <section>\n \n <h3> Key points</h3>\n \n <div>\n <ul>\n \n <li>Study involved 427 women with HIV.</li>\n \n <li>Identified 245 aberrant DNA methylation sites and 85 methylation regions in CD4+ T cells linked to the HIV-1 reservoir.</li>\n \n <li>Highlighted genes are involved in viral replication, immune defence, and host genome integration.</li>\n \n <li>Findings suggest potential molecular targets for eradication strategies.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 3","pages":""},"PeriodicalIF":7.9000,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70267","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Translational Medicine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ctm2.70267","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 0

Abstract

Background

The HIV-1 reservoir in CD4+ T cells (HR_CD4) pose a major challenge to curing HIV, with many of its mechanisms still unclear. HIV-1 DNA integration and immune responses may alter the host's epigenetic landscape, potentially silencing HIV-1 replication.

Methods

This study used bisulphite capture DNA methylation sequencing in CD4+ T cells from the blood of 427 virally suppressed women with HIV to identify differentially methylated sites and regions associated with HR_CD4.

Results

The average total HR_CD4 size was 1409 copies per million cells, with most proviruses defective and only a small proportion intact. The study identified 245 differentially methylated CpG sites and 85 regions linked to HR_CD4 size, with 52% of significant sites in intronic regions. Genes associated with HR_CD4 were involved in viral replication, HIV-1 latency and cell growth and apoptosis. HR_CD4 size was inversely related to DNA methylation of interferon signalling genes and positively associated with methylation at known HIV-1 integration sites. HR_CD4-associated genes were enriched on the pathways related to immune defence, transcription repression and host–virus interactions.

Conclusions

These findings suggest that HIV-1 reservoir is linked to aberrant DNA methylation in CD4+ T cells, offering new insights into epigenetic mechanisms of HIV-1 latency and potential molecular targets for eradication strategies.

Key points

Study involved 427 women with HIV.
Identified 245 aberrant DNA methylation sites and 85 methylation regions in CD4+ T cells linked to the HIV-1 reservoir.
Highlighted genes are involved in viral replication, immune defence, and host genome integration.
Findings suggest potential molecular targets for eradication strategies.

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

Clinical and Translational Medicine Multiple-

CiteScore

15.90

自引率

1.90%

发文量

450

审稿时长

4 weeks

期刊介绍： Clinical and Translational Medicine (CTM) is an international, peer-reviewed, open-access journal dedicated to accelerating the translation of preclinical research into clinical applications and fostering communication between basic and clinical scientists. It highlights the clinical potential and application of various fields including biotechnologies, biomaterials, bioengineering, biomarkers, molecular medicine, omics science, bioinformatics, immunology, molecular imaging, drug discovery, regulation, and health policy. With a focus on the bench-to-bedside approach, CTM prioritizes studies and clinical observations that generate hypotheses relevant to patients and diseases, guiding investigations in cellular and molecular medicine. The journal encourages submissions from clinicians, researchers, policymakers, and industry professionals.