Epitranscriptomic control of viral infection: YTHDF2 at the crossroads of host-virus interactions

N6-methyladenosine (m6A) is one of the most prevalent and dynamic internal RNA modifications, playing a crucial role in regulating gene expression and cancer progression. This epitranscriptomic mark is co-transcriptionally deposited by m6A writers, recognised by reader proteins, and removed by erasers. In recent years, a wide range of viruses have been shown to carry m6A modifications within their RNA genomes or transcripts, which interact with the host cell's m6A machinery to influence the viral life cycle. The field of viral epitranscriptomics has emerged to explore how such modifications impact viral gene expression, replication, and the evasion or modulation of host immune responses. Notably, m6A marks can enhance viral RNA stability through interaction with YTHDF2, a major m6A reader protein. Interest in YTHDF2 has grown due to its roles in RNA metabolism, disease progression, and therapeutic potential. However, its effect on viral replication is complex and context-dependent, exhibiting both proviral and antiviral functions under different cellular environments. This review highlights current insights into how YTHDF2 modulates the replication of various viruses and discusses its broader implications in host-virus interactions.