N 6 -Methyladenosine RNA Modification in Host Cells Regulates Peste des Petits Ruminants Virus Replication

N -methyladenosine (m A) modification is a major RNA epigenetic regulatory mechanism. The dynamics of m A levels in viral genomic RNA and their mRNAs have been shown to have either pro- or antiviral functions, and therefore, m A modifications influence virus-host interactions. Currently, no reports are available on the effect of m A modifications in the genome of (PPRV). In the present study, we took PPRV as a model for nonsegmented negative-sense single-stranded RNA viruses and elucidate the role of m A modification on viral replication. We detected m A-modified sites in the mRNA of the virus and host cells, as well as the PPRV RNA genome. Further, it was found that the level of m A modification in host cells alters the viral gene expression. Knockdown of the METTL3 and FTO genes (encoding the m A RNA modification writer and eraser proteins, respectively) results in alterations of the levels of m A RNA modifications in the host cells. Experiments using these genetically modified clones of host cells infected with PPRV revealed that both higher and lower m A RNA modification in the host cells negatively affect PPRV replication. We found that m A-modified viral transcripts had better stability and translation efficiency compared to the unmodified mRNA. Altogether, from these data, we conclude that the m A modification of RNA regulates PPRV replication. These findings contribute toward a way forward for developing novel antiviral strategies against PPRV by modulating the dynamics of host m A RNA modification. Peste des petits ruminants virus (PPRV) causes a severe disease in sheep and goats. PPRV infection is a major problem, causing significant economic losses to small ruminant farmers in regions of endemicity. N -methyladenosine (m A) is an important RNA modification involved in various functions, including virus-host interactions. In the present study, we used stable clones of Vero cells, having knocked down the genes encoding proteins involved in dynamic changes of the levels of m A modification. We also used small-molecule compounds that interfere with m A methylation. This resulted in a platform of host cells with various degrees of m A RNA modification. The host cells with these different microenvironments were useful for studying the effect of m A RNA modification on the expression of viral genes and viral replication. The results pinpoint the level of m A modifications that facilitate the maximum replication of PPRV. These findings will be useful in