Host microRNA miR-1307 suppresses foot-and-mouth disease virus replication by promoting VP3 degradation and enhancing innate immune response

Abstract

MicroRNAs (miRNAs) play important regulatory roles during interactions between virus pathogens and host cells, but whether and how they work in the case of foot-and-mouth disease virus (FMDV) is less understood. Based on a microarray-based miRNA profiling in the porcine kidney cell line PK-15, we identified 36 differentially expressed host miRNAs at the early stage of FMDV infection, among which miR-1307 was significantly induced. Functional characterization demonstrated that miR-1307 attenuated FMDV replication. Further experiments proved that miR-1307 specifically promoted the degradation of the viral structural protein VP3 indirectly through proteasome pathway. Moreover, innate immune signaling was activated and expression of immune responsive genes was significantly enhanced in the miR-1307-overexpressing clones. Together, our data demonstrated that miR-1307 suppresses FMDV replication by destabilizing VP3 and enhancing host immune response. Importantly, subcutaneous injection of miR-1307 agomir delayed the FMDV-induced lethality in suckling mice, exhibiting its therapeutic potential to control foot-and-mouth disease (FMD).

Keywords: Foot-and-mouth disease virus; Immune response; VP3; miR-1307.