When animal viruses meet N6-methyladenosine (m6A) modifications: for better or worse?

Abstract

N⁶-methyladenosine (m⁶A) is a prevalent and dynamic RNA modification, critical in regulating gene expression. Recent research has shed light on its significance in the life cycle of viruses, especially animal viruses. Depending on the context, these modifications can either enhance or inhibit the replication of viruses. However, research on m⁶A modifications in animal virus genomes and the impact of viral infection on the host cell m⁶A landscape has been hindered due to the difficulty of detecting m⁶A sites at a single-nucleotide level. This article summarises the methods for detecting m⁶A in RNA. It then discusses the progress of research into m⁶A modification within animal viruses' infections, such as influenza A virus, porcine epidemic diarrhoea virus, porcine reproductive, and respiratory syndrome virus. Finally, the review explores how m⁶A modification affects the following three aspects of the replication of animal RNA viruses: the regulation of viral genomic RNA function, the alteration of the m⁶A landscape in cells after viral infection, and the modulation of antiviral immunity through m⁶A modification. Research on m⁶A modifications in viral RNA sheds light on virus-host interactions at a molecular level. Understanding the impact of m⁶A on viral replication can help identify new targets for antiviral drug development and may uncover novel regulatory pathways that could potentially enhance antiviral immune responses.