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

Xingya Wang; Ning Kong; Chen Wang; Wenzhen Qin; Xinyu Yang; Hai Yu; Wu Tong; Guangzhi Tong; Lin Li; Hao Zheng; Tongling Shan; Xuelan Liu

doi:10.1016/j.ijbiomac.2024.138826

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

Int J Biol Macromol. 2024 Dec 16:138826. doi: 10.1016/j.ijbiomac.2024.138826. Online ahead of print.

Authors

Xingya Wang¹, Ning Kong², Chen Wang³, Wenzhen Qin³, Xinyu Yang³, Hai Yu², Wu Tong², Guangzhi Tong², Lin Li⁴, Hao Zheng⁵, Tongling Shan⁶, Xuelan Liu⁷

Affiliations

¹ Animal-derived Food Safety Innovation Team, Anhui Agricultural University, Hefei 230036, China; Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.
² Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China.
³ Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.
⁴ Animal-derived Food Safety Innovation Team, Anhui Agricultural University, Hefei 230036, China.
⁵ Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China. Electronic address: [email protected].
⁶ Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China. Electronic address: [email protected].
⁷ Animal-derived Food Safety Innovation Team, Anhui Agricultural University, Hefei 230036, China; Anhui Province Key Lab of Veterinary Pathobiology and Disease Control, Anhui Agricultural University, Hefei 230036, China. Electronic address: [email protected].

PMID: 39694377
DOI: 10.1016/j.ijbiomac.2024.138826

Abstract

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.

Keywords: HNRNPH1; JEV; NS3; Translation regulation element.