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

N-methyladenosine (mA) modification is a major RNA epigenetic regulatory mechanism. The dynamics of mA levels in viral genomic RNA and their mRNAs have been shown to have either pro- or antiviral functions, and therefore, mA modifications influence virus-host interactions. Currently, no reports are available on the effect of mA 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 mA modification on viral replication. We detected mA-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 mA modification in host cells alters the viral gene expression. Knockdown of the METTL3 and FTO genes (encoding the mA RNA modification writer and eraser proteins, respectively) results in alterations of the levels of mA RNA modifications in the host cells. Experiments using these genetically modified clones of host cells infected with PPRV revealed that both higher and lower mA RNA modification in the host cells negatively affect PPRV replication. We found that mA-modified viral transcripts had better stability and translation efficiency compared to the unmodified mRNA. Altogether, from these data, we conclude that the mA 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 mA 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 (mA) 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 mA modification. We also used small-molecule compounds that interfere with mA methylation. This resulted in a platform of host cells with various degrees of mA RNA modification. The host cells with these different microenvironments were useful for studying the effect of mA RNA modification on the expression of viral genes and viral replication. The results pinpoint the level of mA modifications that facilitate the maximum replication of PPRV. These findings will be useful in increasing the virus titers in cultured cells needed for the economical development of the vaccine. Furthermore, the findings have guiding significance for the development of novel antiviral strategies for limiting PPRV replication in infected animals.