A new area of HIV-1 research revolves around the issue of modifications of individual bases on viral mRNAs that affect mRNA expression and/or function, referred to as epitranscriptomic gene regulation. The most common co-transcriptional modification of mRNAs is addition of a methyl group to the N6 position of adenosine to give an “m6A” residue. These are then bound in the cytoplasm by the m6A reader proteins YTHDF1, 2 and 3. We have recently precisely mapped sites of m6A addition on the HIV-1 genome and have shown that m6A substantially increases HIV-1 mRNA abundance and gene expression. As a result, inhibition of m6A addition, or blocking YTHDF protein binding to m6A, inhibits viral gene expression. We are currently seeking to determine exactly how m6A affects HIV-1 replication and whether other nuclear viruses, such as the retrovirus murine leukemia virus (MLV) and the orthomyxovirus influenza A virus, also utilize m6A to facilitate some aspect of their replication cycle.