Porcine epidemic diarrhea virus suppresses DHX9-mediated antiviral transcription through its nucleocapsid protein.

Porcine epidemic diarrhea virus (PEDV) causes an enteric disease in piglets and leads to economic losses in the swine industry. Antiviral defense depends on interferon responses, yet how PEDV suppresses antiviral transcription remains incompletely understood. We show that DExH-box helicase 9 (DHX9) functions as a host restriction factor that is antagonized by the PEDV nucleocapsid (N) protein. PEDV infection decreases DHX9 protein abundance without affecting DHX9 transcript levels. DHX9 overexpression restricts PEDV replication, whereas DHX9 depletion enhances viral replication. Mechanistically, DHX9 forms a transcriptional complex with signal transducer and activator of transcription 1 (STAT1) and RNA polymerase II to promote interferon-stimulated gene (ISG) expression. The PEDV N protein binds the STAT1-interacting region of DHX9 and disrupts assembly of the DHX9-STAT1-RNA polymerase II complex, suppressing antiviral transcription. In parallel, the N protein promotes ubiquitination and proteasome-dependent degradation of DHX9 by enhancing its interaction with the E3 ubiquitin ligase MDM2, attenuating STAT1-associated antiviral signaling. Together, these findings identify DHX9 as a regulator of antiviral transcription during PEDV infection and reveal how PEDV suppresses antiviral responses through disruption and degradation of DHX9. This work provides insights into coronavirus immune evasion and suggests that the PEDV N-DHX9 axis may represent a target for antiviral strategies.