The role of N6-methyladenosine (m6A) mRNA modifications in herpesvirus infections

Herpesviruses, a family of large enveloped DNA viruses, establish persistent infections in a wide range of hosts. This characteristic requires an intricate network of interactions with their hosts and host cells. In recent years, the interplay between herpesviruses and the epitranscriptome-chemical modifications in transcripts that may affect mRNA biology and fate-has emerged as a novel aspect of herpesvirus-host interactions. In particular, herpesviruses display different mechanisms to modulate and usurp the most abundant mRNA modification, N6-methyladenosine or m(6)A. Some herpesviruses interfere with m(6)A methylation of transcripts, while others enhance or take advantage of m(6)A methylation of viral and/or cellular transcripts. In many cases, herpesviruses appear to modulate the m(6)A methylation process to suppress the antiviral host response. This review highlights the strategies used by members of the different herpesvirus subfamilies to manipulate host m(6)A mediators and how these contribute to virus replication and the antiviral host response. Research aimed at deciphering the interaction of herpesviruses with the m(6)A epitranscriptome not only may lead to new avenues in the design of antiviral and immunomodulatory strategies, but also provides new insights in the regulation and the role of m(6)A transcript methylation in general.