N6-methyladenosine epitranscriptomic remodeling: Dynamic landscape and functional analysis of host RNA methylation...

N6-methyladenosine (m⁶A) modification, the most abundant form of RNA methylation identified to date, plays a critical role in RNA metabolism and function. Porcine reproductive and respiratory syndrome virus (PRRSV), a severe viral pathogen, causes substantial economic losses to the global swine industry. While m⁶A is known to play roles in multiple virus replication cycles and modulate host antiviral responses, its regulatory mechanisms in PRRSV infection and the resultant host immune responses remain incompletely understood. In this study, we demonstrated that PRRSV infection induced m⁶A modification of host mRNAs by using molecular assays and m⁶A-seq. Meanwhile, we observed the expression and subcellular localization of m⁶A methyltransferases, demethylases, and YTH domain-containing proteins were activated during PRRSV infection. Functional validation revealed that these m⁶A regulators participate in modulating viral replication. Notably, our findings uncovered that m⁶A methylation was occurred in many host proteins, such as zinc finger proteins and antiviral transcription factors, and regulated their transcriptional level following viral infection, suggesting their potential roles in antiviral defense. Additionally, the MAPK signaling pathway and IL-11 signaling pathway were identified as putative initial targets of m⁶A-mediated epigenetic regulation during PRRSV infection. These results revealed a comprehensive dynamic m⁶A landscape during PRRSV infection, and provide novel insights into virus-host interactions.