m⁶A RNA Modification Controls HTLV‐1 Tax and Host Gene Expression

Human T‐cell Leukemia Virus Type 1 (HTLV‐1) is a pathogenic human retrovirus that is responsible for intractable diseases such as adult T‐cell leukemia–lymphoma (ATL), a malignancy with a poor patient prognosis. Although recent studies have delineated several genomic, epigenomic, and transcriptomic abnormalities associated with HTLV‐1, to date the importance of epitranscriptomic modifications, particularly N 6 ‐methyladenosine (m 6 A), remains unclear. Here, we showed that the HTLV‐1 RNA genome undergoes m 6 A modification, thereby suggesting that these modifications act as bidirectional regulators of both viral and host processes. Moreover, targeted depletion of m 6 A modification within the viral transactivator HTLV‐1 Tax resulted in markedly destabilized Tax mRNA, attenuated Tax protein abundance, and suppression of downstream expression of host genes including IL2RA and TXN . Overall, these findings suggest that m 6 A methylation is an essential determinant of the HTLV‐1 life cycle, and understanding it may offer mechanistic insight into viral latency and present novel avenues for therapeutic intervention and prophylaxis.