| Summary: | Epitranscriptomic RNA modifications play a crucial role in the posttranscriptional regulation of gene expression. <i>N</i><sup>6</sup>-methyladenosine (m<sup>6</sup>A) is the most prevalent internal modification of eukaryotic RNA and plays a pivotal role in RNA fate. RNA m<sup>6</sup>A modification is regulated by a group of cellular proteins, methyltransferases (writers) and demethylases (erasers), which add and remove the methyl group from adenosine, respectively. m<sup>6</sup>A modification is recognized by a group of cellular RNA-binding proteins (readers) that specifically bind to m<sup>6</sup>A-modified RNA, mediating effects on RNA stability, splicing, transport, and translation. The functional significance of m<sup>6</sup>A modification of viral and cellular RNA is an active area of virology research. In this review, we summarize and analyze the current literature on m<sup>6</sup>A modification of HIV-1 RNA, the multifaceted functions of m<sup>6</sup>A in regulating HIV-1 replication, and the role of viral RNA m<sup>6</sup>A modification in evading innate immune responses to infection. Furthermore, we briefly discuss the future directions and therapeutic implications of mechanistic studies of HIV-1 epitranscriptomic modifications.
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