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Antiretroviral therapy suppresses RNA N6-methyladenosine modification in peripheral blood mononuclear cells from HIV-1-infected individuals.
AIDS Research and Human Retroviruses 2024 May 16
RNA N6-methyladenosine (m6A) modification is important for regulating gene expression and innate immune responses to viral infection. HIV-1 in vitro infection induces a significant increase in m6A modification of cellular RNA; however, whether m6A levels of cellular RNA are affected by HIV-1 replication or by antiretroviral therapy (ART) in infected individuals remain unknown. Using dot blot or ELISA, we measured RNA m6A levels of peripheral blood monocytic cells (PBMCs) from healthy donors or HIV-1-infected individuals with or without ART. Using an RT-qPCR array, we quantified expression levels of 84 type-I interferon (IFN-I)-responsive genes in PBMCs from some individuals of these three groups. RNA m6A levels in PBMCs from HIV-1 viremic patients (n=10) were significantly higher (p ≤0.0001) compared to ART-treated individuals (n=22) or 1.5-fold higher compared to healthy donors (n=14). However, the increase in RNA m6A levels did not correlate with changes in the expression of ten m6A-regulatory genes. We found significant upregulation or downregulation in the expression of several IFN-I-responsive genes from HIV-1 viremic patients (n=4) or ART-treated patients (n=6) compared to healthy donors (n=5). Our results suggest that post-transcriptional m6A modification may contribute to the regulation of IFN-I-responsive gene expression during HIV-1 infection and ART.
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