Vpr driving DNA methylation variation of CD4 + T cells in HIV-1 infection.
Accessory protein Vpr
DNA methylation
HIV-1
WGBS
Journal
Virology journal
ISSN: 1743-422X
Titre abrégé: Virol J
Pays: England
ID NLM: 101231645
Informations de publication
Date de publication:
26 Apr 2024
26 Apr 2024
Historique:
received:
04
02
2024
accepted:
11
04
2024
medline:
27
4
2024
pubmed:
27
4
2024
entrez:
26
4
2024
Statut:
epublish
Résumé
Despite the existence of available therapeutic interventions for HIV-1, this virus remains a significant global threat, leading to substantial morbidity and mortality. Within HIV-1-infected cells, the accessory viral protein r (Vpr) exerts control over diverse biological processes, including cell cycle progression, DNA repair, and apoptosis. The regulation of gene expression through DNA methylation plays a crucial role in physiological processes, exerting its influence without altering the underlying DNA sequence. However, a thorough examination of the impact of Vpr on DNA methylation in human CD4 + T cells has not been conducted. In this study, we employed base-resolution whole-genome bisulfite sequencing (WGBS), real-time quantitative RCR and western blot to explore the effect of Vpr on DNA methylation of host cells under HIV-1 infection. We observed that HIV-1 infection leads to elevated levels of global DNA methylation in primary CD4 + T cells. Specifically, Vpr induces significant modifications in DNA methylation patterns, particularly affecting regions within promoters and gene bodies. These alterations notably influence genes related to immune-related pathways and olfactory receptor activity. Moreover, Vpr demonstrates a distinct ability to diminish the levels of methylation in histone genes. These findings emphasize the significant involvement of Vpr in regulating transcription through the modulation of DNA methylation patterns. Together, the results of this investigation will considerably enhance our understanding of the influence of HIV-1 Vpr on the DNA methylation of host cells, offer potential avenues for the development of more effective treatments.
Sections du résumé
BACKGROUND
BACKGROUND
Despite the existence of available therapeutic interventions for HIV-1, this virus remains a significant global threat, leading to substantial morbidity and mortality. Within HIV-1-infected cells, the accessory viral protein r (Vpr) exerts control over diverse biological processes, including cell cycle progression, DNA repair, and apoptosis. The regulation of gene expression through DNA methylation plays a crucial role in physiological processes, exerting its influence without altering the underlying DNA sequence. However, a thorough examination of the impact of Vpr on DNA methylation in human CD4 + T cells has not been conducted.
METHODS
METHODS
In this study, we employed base-resolution whole-genome bisulfite sequencing (WGBS), real-time quantitative RCR and western blot to explore the effect of Vpr on DNA methylation of host cells under HIV-1 infection.
RESULTS
RESULTS
We observed that HIV-1 infection leads to elevated levels of global DNA methylation in primary CD4 + T cells. Specifically, Vpr induces significant modifications in DNA methylation patterns, particularly affecting regions within promoters and gene bodies. These alterations notably influence genes related to immune-related pathways and olfactory receptor activity. Moreover, Vpr demonstrates a distinct ability to diminish the levels of methylation in histone genes.
CONCLUSIONS
CONCLUSIONS
These findings emphasize the significant involvement of Vpr in regulating transcription through the modulation of DNA methylation patterns. Together, the results of this investigation will considerably enhance our understanding of the influence of HIV-1 Vpr on the DNA methylation of host cells, offer potential avenues for the development of more effective treatments.
Identifiants
pubmed: 38671522
doi: 10.1186/s12985-024-02363-5
pii: 10.1186/s12985-024-02363-5
doi:
Substances chimiques
vpr Gene Products, Human Immunodeficiency Virus
0
vpr protein, Human immunodeficiency virus 1
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
97Subventions
Organisme : National Key R&D Program of China
ID : 2021YFC2301903
Organisme : National Natural Science Foundation of China
ID : 32070159
Organisme : National Natural Science Foundation of China
ID : 82302514
Organisme : Science and Technology Projects of Guangdong Province of China
ID : 2021B1212030012
Informations de copyright
© 2024. The Author(s).
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