Swine interferon-induced transmembrane proteins inhibit porcine epidemic diarrhea virus replication

Porcine epidemic diarrhea (PED) caused by porcine epidemic diarrhea virus (PEDV) has significantly harmed the global pig industry economically. Interferons can induce the expression of interferon-stimulated genes (ISGs) that encode various natural antiviral immune effectors. Notably, swine interferon-induced transmembrane proteins (SwIFITMs) have not been thoroughly investigated in the context of PEDV. In the present research, we explored the anti-PEDV effects of SwIFITMs. Both interferon and PEDV were found to upregulate swine IFITM mRNA levels. Swine IFITM knockdown results showed that SwIFITM1a, -1b, and -2 most significantly reduced PEDV replication. By overexpressing SwIFITMs and establishing a SwIFITM-expressing Vero cell line, we identified SwIFITM2 as having the most pronounced anti-PEDV effect. SwIFITM2 inhibited PEDV entry phase. Additionally, SwIFITM2 interacted with PEDV S2 and N proteins in a dose-dependent manner. Furthermore, it exhibited high co-localization with caveolin-1, while demonstrating the lowest co-localization ratio with clathrin. Upon infection with PEDV, the co-localization of caveolin-1 and PEDV S2 or N protein significantly increased compared with control in the presence of SwIFITM2, indicating that SwIFITM2 may play an antiviral role by confining PEDV within caveolin-1. This study elucidates the anti-PEDV mechanisms of SwIFITMs, providing critical insights into their potential roles in viral pathogenesis and host defense.