Aberrant DNA methylation of genes regulating CD4+ T cell HIV‐1 reservoir in women with HIV
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...
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Wiley
2025-03-01
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| Series: | Clinical and Translational Medicine |
| Online Access: | https://doi.org/10.1002/ctm2.70267 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ke Xu |
| collection | DOAJ |
| description | 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. 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. |
| format | Article |
| id | doaj-art-6cf287c18e1a407aaa0aaa6b4aa79dd6 |
| institution | OA Journals |
| issn | 2001-1326 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
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| series | Clinical and Translational Medicine |
| spelling | doaj-art-6cf287c18e1a407aaa0aaa6b4aa79dd62025-08-20T01:52:18ZengWileyClinical and Translational Medicine2001-13262025-03-01153n/an/a10.1002/ctm2.70267Aberrant DNA methylation of genes regulating CD4+ T cell HIV‐1 reservoir in women with HIVKe Xu0Xinyu Zhang1Kesava Asam2Bryan C. Quach3Grier P. Page4Deborah Konkle‐Parker5Claudia Martinez6Cecile D. Lahiri7Elizabeth F. Topper8Mardge H. Cohen9Seble G. Kassaye10Jack DeHovitz11Mark H. Kuniholm12Nancie M. Archin13Amir Valizadeh14Phyllis C. Tien15Vincent C. Marconi16Dana B. Hancock17Eric O. Johnson18Bradley E. Aouizerat19Department of Psychiatry, School of Medicine Yale University New Haven Connecticut USADepartment of Psychiatry, School of Medicine Yale University New Haven Connecticut USADepartment of Oral and Maxillofacial Surgery New York University New York New York USAGenOmics and Translational Research Center RTI International, Research Triangle Park North Carolina USAGenOmics and Translational Research Center RTI International, Research Triangle Park North Carolina USASchools of Nursing, Medicine, and Population Health University of Mississippi Medical Center Jackson Mississippi USAMiller School of Medicine, Division of Cardiovascular Medicine University of Miami Miami Florida USADepartment of Medicine, Division of Infectious Diseases Emory University School of Medicine Atlanta Georgia USADepartment of Epidemiology, Bloomberg School of Public Health Johns Hopkins University Baltimore Maryland USADepartment of Medicine, Stroger Hospital Cook County Health System Chicago Illinois USADepartment of Medicine, Division of Infectious Diseases Georgetown University Washington District of Columbia USADepartment of Medicine, Division of Infectious Diseases Downstate Health Sciences University Brooklyn New York USADepartment of Epidemiology and Biostatistics University at Albany, State University of New York Rensselaer New York USAUNC HIV Cure Center University of North Carolina at Chapel Hill School of Medicine Chapel Hill North Carolina USADepartment of Psychiatry, School of Medicine Yale University New Haven Connecticut USADepartment of Medicine University of California at San Francisco San Francisco California USADepartment of Medicine, Division of Infectious Diseases Emory University School of Medicine Atlanta Georgia USAGenOmics and Translational Research Center RTI International, Research Triangle Park North Carolina USAGenOmics and Translational Research Center RTI International, Research Triangle Park North Carolina USADepartment of Oral and Maxillofacial Surgery New York University New York New York USAAbstract 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. 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.https://doi.org/10.1002/ctm2.70267 |
| spellingShingle | 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 Aberrant DNA methylation of genes regulating CD4+ T cell HIV‐1 reservoir in women with HIV Clinical and Translational Medicine |
| title | Aberrant DNA methylation of genes regulating CD4+ T cell HIV‐1 reservoir in women with HIV |
| title_full | Aberrant DNA methylation of genes regulating CD4+ T cell HIV‐1 reservoir in women with HIV |
| title_fullStr | Aberrant DNA methylation of genes regulating CD4+ T cell HIV‐1 reservoir in women with HIV |
| title_full_unstemmed | Aberrant DNA methylation of genes regulating CD4+ T cell HIV‐1 reservoir in women with HIV |
| title_short | Aberrant DNA methylation of genes regulating CD4+ T cell HIV‐1 reservoir in women with HIV |
| title_sort | aberrant dna methylation of genes regulating cd4 t cell hiv 1 reservoir in women with hiv |
| url | https://doi.org/10.1002/ctm2.70267 |
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