Epigenome-wide characterization reveals aberrant DNA methylation of host genes regulating CD4+ T cell HIV-1 reservoir size in women with HIV Article Swipe
Ke Xu
,
Xinyu Zhang
,
Kesava Asam
,
Bryan C. Quach
,
Grier P. Page
,
Deborah Konkle‐Parker
,
Claudia Martinez
,
Cecile D. Lahiri
,
Elizabeth Topper
,
Mardge H. Cohen
,
Seble 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
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1101/2024.07.26.24311074
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1101/2024.07.26.24311074
The underlying mechanism of the HIV-1 reservoir, a major barrier to an HIV cure, is largely unknown. The integration of HIV-1 DNA and immune defense mechanisms can disrupt the host epigenetic landscape, potentially silencing HIV-1 replication. Using bisulfite capture DNA methylation sequencing, we profiled approximately 3.2 million CpG sites in CD4 + T cells isolated from the blood of 427 virally suppressed women with HIV. The average total CD4 + T cell HIV-1 Reservoir (HR CD4 ) size was 1,409 copies per million cells. Most proviruses were defective with only a small proportion being intact. We found 245 differentially methylated positions (CpG sites) and 85 methylated regions associated with the total HR CD4 size. Notably, 52% of significant methylation sites were in intronic regions. HR CD4 -associated genes were involved in viral replication (e.g., ISG15 ), HIV-1 latency (e.g., MBD2 ), and cell growth and apoptosis (e.g., IRF9 ). A subset of the identified genes with aberrant methylation was an established target of HIV-1 integration (e.g., NFIA, SPPL3, DLEU2, ELMSAN1 ). Overall, HR CD4 size was inversely associated with DNA methylation of interferon signaling genes and positively associated with methylation at established HIV-1 integration sites. HR CD4 -associated genes were enriched in pathways including immune defense against the virus (i.e., interferon-α response and interferon-γ response), DNA binding transcription repression, and host-virus interaction such as Tau protein binding. Together, our results show that epigenomic alterations in CD4 + T cells are associated with total HIV-1 reservoir size, offering new insights into HIV-1 latency and may provide potential molecular targets for future HIV-1 eradication strategies.
Related Topics
Concepts
DNA methylation
Biology
CpG site
Methylation
Epigenomics
Epigenetics
Epigenome
Gene
Interferon
Viral replication
Molecular biology
Virology
Virus
Genetics
Gene expression
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2024.07.26.24311074
- https://www.medrxiv.org/content/medrxiv/early/2024/07/27/2024.07.26.24311074.full.pdf
- OA Status
- green
- References
- 54
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4401045639
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4401045639Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2024.07.26.24311074Digital Object Identifier
- Title
-
Epigenome-wide characterization reveals aberrant DNA methylation of host genes regulating CD4+ T cell HIV-1 reservoir size in women with HIVWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-07-27Full publication date if available
- Authors
-
Ke Xu, Xinyu Zhang, Kesava Asam, Bryan C. Quach, Grier P. Page, Deborah Konkle‐Parker, Claudia Martinez, Cecile D. Lahiri, Elizabeth Topper, Mardge H. Cohen, Seble 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. AouizeratList of authors in order
- Landing page
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https://doi.org/10.1101/2024.07.26.24311074Publisher landing page
- PDF URL
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https://www.medrxiv.org/content/medrxiv/early/2024/07/27/2024.07.26.24311074.full.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
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-
greenOpen access status per OpenAlex
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https://www.medrxiv.org/content/medrxiv/early/2024/07/27/2024.07.26.24311074.full.pdfDirect OA link when available
- Concepts
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DNA methylation, Biology, CpG site, Methylation, Epigenomics, Epigenetics, Epigenome, Gene, Interferon, Viral replication, Molecular biology, Virology, Virus, Genetics, Gene expressionTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
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54Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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