Dynamic interplay between RNA N6-methyladenosine modification and porcine reproductive and respiratory syndrome virus infection

N-6-methyladenosine (m(6)A) has attracted significant attention for its role in regulating the complex interaction between viruses and host cells. Porcine reproductive and respiratory syndrome virus (PRRSV) is a significant pathogen affecting swine health worldwide. Here, we first identified seven m(6)A-enriched peaks in PRRSV genomic RNA by m(6)A RNA immunoprecipitation sequencing (m(6)A-seq). Moreover, functional analyses revealed a positive correlation between the m(6)A modification level and PRRSV replication. Treatment with the universal methylation inhibitor 3-deazaadenosine (3-DAA) effectively suppressed PRRSV replication in a dose-dependent manner. Furthermore, m(6)A-seq was also used to determine the m(6)A landscape of the transcriptome in PAMs infected with pandemic or highly pathogenic PRRSV strains. Among the 4677 transcripts exhibiting altered m(6)A modification levels, the MAPK14 gene and the p38/MAPK signalling pathway emerged as preliminary targets of m(6)A-mediated epigenetic regulation during PRRSV infection. These findings provide new insights into the epigenetic mechanisms underlying PRRSV infection and may facilitate the development of anti-PRRSV therapeutics.