Epitranscriptomic m ⁶ A modifications during reactivation of HIV-1 latency in CD4 ⁺ T cells

RNA m⁶A modification is important for regulating gene expression and innate immune responses to HIV-1 infection. However, the functional significance of m⁶A modification during HIV-1 latency reactivation is unknown. To address this important question, in this study, we used established cellular models of HIV-1 latency, m⁶A-specific sequencing at single-base resolution, and functional assays. We demonstrate that HIV-1 latency reversal leads to increased levels of cellular m⁶A modification, correlates with cellular m⁶A levels, and is dependent on the catalytic activity of the m⁶A methyltransferase enzyme. We also identified cellular genes that are differentially m⁶A-modified during HIV-1 reactivation, as well as the sites of m⁶A within HIV-1 RNA. Our novel findings point toward a significant role for m⁶A modification in HIV-1 latency reversal.