CAV1 up-regulated by peste des petits ruminants virus nucleocapsid protein impairs type I IFN response by cholesterol synthesis.

Peste des petits ruminants virus (PPRV) is a highly contagious pathogen that infects domestic and wild small ruminants, causing high mortality worldwide. PPRV has evolved multiple strategies to suppress the host antiviral immune response, thereby promoting viral replication. In this study, we demonstrate that caveolin-1 (CAV1) promotes PPRV replication. Mechanistically, CAV1 inhibits IFN-β production, ISG expression, and the IFN signaling pathway by promoting cholesterol synthesis. Importantly, we reveal that PPRV infection upregulates cellular CAV1 protein levels, and the viral nucleocapsid (N) protein alone is sufficient to promote CAV1 expression. Furthermore, the N protein interacts with CAV1; amino acids 106-210 of N constitute the critical binding region. We also show that N acts synergistically with CAV1 to inhibit type I IFN production. Collectively, our findings elucidate the mechanism by which the PPRV N protein hijacks CAV1-a host factor that is associated with cholesterol synthesis-to antagonize type I IFN production. This study provides a theoretical framework for understanding PPRV pathogenesis, particularly the role of the N protein in immune suppression, and reveals potential targets for antiviral therapeutic development.