Dual role of RBM3 in PEDV infection: stabilization of viral RNA and upregulation of the entry factor HSPA5

Abstract

RBM3, a member of the cold-shock protein family, functions as an RNA chaperone that stabilizes target transcripts by binding to their untranslated regions (UTRs). Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus that poses a serious threat to the swine industry, and its replication heavily depends on its genomic and subgenomic RNAs, making these RNAs potential targets for host RNA-binding proteins. In this study, we show that RBM3 promotes PEDV replication through a dual mechanism. On one hand, RBM3 exhibits a binding preference for the viral 3'UTR, which prolongs the half-life of viral RNA and thereby promotes PEDV proliferation. RBM3 also interacts with the PEDV nucleocapsid (N) protein and replication-associated double-stranded RNA (dsRNA) signals, suggesting that RBM3 may be associated with viral replication complexes, though its contribution to their functional integrity remains to be determined. On the other hand, RBM3 increases HSPA5 promoter activity and HSPA5 mRNA levels, linking RBM3 to HSPA5, a host factor known to facilitate PEDV attachment and internalization. These two mechanisms together provide a mechanistic basis for efficient PEDV infection. Our findings identify RBM3 as a positive host regulator of PEDV and establish, for the first time, a functional link between RBM3 and HSPA5, offering new insights into coronavirus-host interactions and suggesting RBM3 as a potential target for antiviral intervention.