Transcriptomic crosstalk between viral and host factors drives aberrant homeostasis of T-cell proliferation and cell death in HIV-infected immunological non-responders - 30/04/24
Summary |
Background |
Immunological non-responders (INRs) among people living with HIV have inherently higher mortality and morbidity rates. The underlying immunological mechanisms whereby failure of immune reconstitution occurs in INRs require elucidation.
Method |
HIV-1 DNA and HIV-1 cell-associated RNA (CA-HIV RNA) quantifications were conducted via RT-qPCR. Transcriptome sequencing (RNA-seq), bioinformatics, and biological verifications were performed to discern the crosstalk between host and viral factors. Flow cytometry was employed to analyze cellular activation, proliferation, and death.
Results |
HIV-1 DNA and CA-HIV RNA levels were observed to be significantly higher in INRs compared to immunological responders (IRs). Evaluation of CD4/CD8 ratios showed a significantly negative correlation with HIV-1 DNA in IRs, but not in INRs. Bioinformatics analyses and biological verifications showed IRF7/INF-α regulated antiviral response was intensified in INRs. PBMCs of INRs expressed significantly more HIV integrase-mRNA (p31) than IRs. Resting (CD4+CD69- T-cells) and activated (CD4+CD69+ T-cells) HIV-1 reservoir harboring cells were significantly higher in INRs, with the co-occurrence of significantly higher cellular proliferation and cell death in CD4+ T-cells of INRs.
Conclusion |
In INRs, the systematic crosstalk between the HIV-1 reservoir and host cells tends to maintain a persistent antiviral response-associated inflammatory environment, which drives aberrant cellular activation, proliferation, and death of CD4+ T-cells.
Le texte complet de cet article est disponible en PDF.Highlights |
• | Higher HIV-1 DNA and CA-HIV RNA in INRs validated in a large cohort. |
• | IRF7/IFN-α-mediated antiviral response intensified in INRs. |
• | HIV-1 integrase-mRNA is the only significantly over-expressed viral gene in INRs. |
• | More resting and activated HIV-1 reservoir cells in INRs. |
• | Higher turnover of CD4+ T-cells and cellular death observed in INRs. |
Keywords : Immunological non-responders, HIV reservoir, Anti-viral response, Viral factor, Cell death
Plan
Vol 88 - N° 5
Article 106151- mai 2024 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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