Aberrant DNA methylation of genes regulating CD4+ T cell HIV‐1 reservoir in women with HIV
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background: The HIV‐1 reservoir in CD4+ T cells (HRCD4) 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 HRCD4. Results: The average total HRCD4 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 HRCD4 size, with 52% of significant sites in intronic regions. Genes associated with HRCD4 were involved in viral replication, HIV‐1 latency and cell growth and apoptosis. HRCD4 size was inversely related to DNA methylation of interferon signalling genes and positively associated with methylation at known HIV‐1 integration sites. HRCD4‐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.
Source: UNC Libraries
DOI: 10.17615/dtcm-ap67
Authors: Lahiri, Cecile D., Martinez, Claudia, Marconi, Vincent C., Konkle‐Parker, Deborah, Tien, Phyllis C., Aouizerat, Bradley E., Page, Grier P., Valizadeh, Amir, Quach, Bryan C., Johnson, Eric O., Kuniholm, Mark H., Hancock, Dana B., DeHovitz, Jack, Archin, Nancie M., Kassaye, Seble G., Asam, Kesava, Cohen, Mardge H., Zhang, Xinyu, Topper, Elizabeth F., Xu, Ke
Institution: University of North Carolina at Chapel Hill
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: Bill and Melinda Gates Foundation, Richard and Susan Smith Family Foundation, United States - Israel Binational Agricultural Research and Development Fund, Prince Sattam bin Abdulaziz University, Comunidad de Madrid, Ministerio de Ciencia, Innovación y Universidades, Göran Gustafssons Stiftelser, Leverhulme Trust, Enterprise Ireland, Deutsche Forschungsgemeinschaft, National Natural Science Foundation of China, Grantová Agentura České Republiky, Islamic Azad University, China Postdoctoral Science Foundation, Ministerio de Economía y Competitividad, Shanghai Municipal Education Commission, Korea Health Industry Development Institute, Natural Science Foundation of Hubei Province, Israel Science Foundation, Vetenskapsrådet, Türkiye Bilimsel ve Teknolojik Araştırma Kurumu, Chengdu Normal University, Ministerio de Ciencia e Innovación, AstraZeneca Australia, Turun Yliopisto, Universität Rostock, Fundación Fero, Turun Yliopistosäätiö, National Institutes of Health, Social Sciences and Humanities Research Council of Canada, Engineering and Physical Sciences Research Council, Japan Society for the Promotion of Science, Science and Engineering Research Board, Agencia Estatal de Investigación, National Key Research and Development Program of China, Fundamental Research Funds for the Central Universities, Guangxi Key Research and Development Program, Center for Innovative Medicine, National Institute on Drug Abuse, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, Kavli Institute for Brain and Mind, University of California, San Diego, Zhejiang Provincial Outstanding Youth Science Foundation, Veterans Affairs Scholarship Program, Key Research and Development Program of Zhejiang Province
OpenAlex ID: W7171051950