Japanese encephalitis virus NS3 captures the protein translation element by interacting with HNRNPH1 to promote viral replication.

Japanese encephalitis caused by Japanese encephalitis virus (JEV) infection leads to the central nervous system disorder in human and swine. Viruses utilize the host protein synthesis mechanisms to efficiently translate their RNAs. Herein, we demonstrated that the host transcription factor SOX10 downregulated an RNA-binding protein heterogeneous nuclear ribonucleoprotein H (HNRNPH1) during JEV infection. We further showed that JEV replication was promoted when HNRNPH1 inhibited RIG-I/MDA5 signal pathway to decrease interferon (IFN) expression. Remarkably, the multifunctional enzyme NS3 of JEV can capture HNRNPH1 to recruit poly A-binding protein cytoplasmic 1 (PABPC1) and RNA-independent eukaryotic translation initiation factor 4F complex (eIF4F), ultimately promoting viral replication. Collectively, our results provide new insights into the mechanism underlying JEV replication via the nonstructural protein NS3, which captures the translation regulation element by interacting with HNRNPH1 to promote viral replication.