N6-methyladenosine modification—a key player in viral infection

Table 1 Mechanism of m⁶A modification occurring in viruses

Type	Virus	Protein	Biological function	Refs.
	SARS-CoV-2	METTL3	Enhance m⁶A modification of SARS-CoV-2 RNA, viral load, and proviral gene expression	[52]
			Interacts with the N region of RdRp	[54]
			Inhibits RIG-I binding to SARS-CoV-2 RNA	[52]
		RBM15	Regulates the expression of multiple target genes	[55]
RNA virus		RBM15	Exacerbates the inflammatory response and promotes cell death signaling pathway in COVID-19	[55]
	HIV-1	METTL3	Promotes Gag protein expression and the level of capsid p24 release	[75]
		METTL14
		YTHDF1-3	Binds with HIV-1 RNA to negatively regulate HIV-1 post-entry infection by blocking viral reverse transcription
	KSHV	YTHDC1	Binds to m⁶A sites on the RTA pre-mRNA	[85]
		FTO	Decrease m⁶A level and enhanced TPA induction of KSHV lytic gene expression	[85]
		YTHDF2	Decrease the half-life of KSHV transcripts	[86]
	EBV	METTL14	Cooperates with EBNA3C to promote cell growth and proliferation	[81]
DNA virus		METTL14	Increases the tumorigenic activity of EBV-transformed cells	[81]
		METTL3	BZLF1 represses METTL3 expression by binding to promoter	[82]
			Promotes the production of progeny virions and expression of the late viral lytic protein BKRF4, BALF4	[28]
			Promotes EBNA2 expression	[83]
		YTHDF1	Promotes the binding of RNA degradation complexes (ZAP, DDX17, and DCP2) to the mRNAs of BZLF1 and BRLF1 to suppress EBV infection and replication	[84]
		YTHDF2	Increases KLF4 mRNA instability	[82]

SARS-CoV-2 severe acute respiratory syndrome coronavirus clade 2, RBM15 RNA-binding motif protein 15, RdRp RNA-dependent RNA polymerase

ISSN: 1689-1392