Emerging roles of biological m⁶A proteins in regulating virus infection: A review

N⁶-methyladenosine (m⁶A) is the most prevalent chemical modifications of intracellular RNA, which recently emerging as a multifaceted effector of viral genomic RNA. As a dynamic process, three groups of biological proteins control the levels of m⁶A modification in eukaryocyte, designed as m⁶A writers, erasers, and readers. The m⁶A writers comprising of methyltransferases complex initiate the modification process. On the contrary, the m⁶A erasers ALKBH5 or FTO abolish the modification through three-step demethylation: m⁶A to N⁶-hydroxymethyl adenosine (hm⁶A), then hm⁶A to N⁶-methyladenosine (f⁶A), and finally f⁶A to adenosine. The known m⁶A readers include the YTH family and the hnRNP family. As m⁶A modification regulates RNA nuclear exportation, stability, and translation, m⁶A proteins commonly participate in virus infection by regulating viral genomic RNA synthesis. Moreover, m⁶A proteins establish molecular linkages between virus genome/viral encode proteins and host cells proteins via their multifunctional roles in cellular RNA metabolism. The m⁶A writers and erasers directly impact interferon expression and macrophage innate immune responses, facilitating them to act as anti-/pro-viral factors. The m⁶A readers enable to alter cell metabolism and stress granules (SGs) production to regulate virus-host interactions. Here, the latest progress of m⁶A proteins in regulating viral infection is reviewed. Demonstrating the roles of m⁶A proteins will enhance the understanding of epigenetic regulation of virus infection and stimulate the development of novel antiviral strategies.