Autophagy mediated degradation of MITA/TBK1/IRF3 by a hnRNP family member attenuates interferon production in fish

Yanwei Zhang; Jing Cen; Haixia Wu; Wa Gao; Zhiying Jia; Mikolaj Adamek; Jun Zou

doi:10.1016/j.fsi.2024.109563

Autophagy mediated degradation of MITA/TBK1/IRF3 by a hnRNP family member attenuates interferon production in fish

Fish Shellfish Immunol. 2024 Jun:149:109563. doi: 10.1016/j.fsi.2024.109563. Epub 2024 Apr 19.

Authors

Yanwei Zhang¹, Jing Cen¹, Haixia Wu¹, Wa Gao¹, Zhiying Jia², Mikolaj Adamek³, Jun Zou⁴

Affiliations

¹ Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, 201306, China; International Research Center for Marine Biosciences, Ministry of Science and Technology, Shanghai Ocean University, Shanghai, 201306, China; National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai, 201306, China.
² Heilongjiang River Fisheries Research Institute, CAFS, Harbin, Heilongjiang Province, 150070, China.
³ Fish Disease Research Unit, Institute for Parasitology, University of Veterinary Medicine Hannover, Hannover, Germany.
⁴ Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, 201306, China; International Research Center for Marine Biosciences, Ministry of Science and Technology, Shanghai Ocean University, Shanghai, 201306, China; National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai, 201306, China; Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao, 266200, China. Electronic address: jzou@shou.edu.cn.

PMID: 38642725
DOI: 10.1016/j.fsi.2024.109563

Abstract

HnRNP A/B belongs to the heterogeneous nuclear ribonucleoprotein (hnRNP) family and plays an important role in regulating viral protein translation and genome replication. Here, we found that overexpression of hnRNP A/B promoted spring viremia of carp virus (SVCV) and cyprinid herpesvirus 3 (CyHV3) replication. Further, hnRNP A/B was shown to act as a negative regulator of type I interferon (IFN) response. Mechanistically, hnRNP A/B interacted with MITA, TBK1 and IRF3 to initiate their degradation. In addition, hnRNP A/B bound to the kinase domain of TBK1, the C terminal domain of MITA and IAD domain of IRF3, and the RRM1 domain of hnRNP A/B bound to TBK1, RRM2 domain bound to IRF3 and MITA. Our study provides novel insights into the functions of hnRNP A/B in regulating host antiviral response.

Keywords: Autophagy; HnRNP A/B; Interferon; Virus.

MeSH terms

Animals
Carps / genetics
Carps / immunology
Fish Diseases* / immunology
Fish Diseases* / virology
Fish Proteins* / genetics
Fish Proteins* / immunology
Fish Proteins* / metabolism
Herpesviridae / physiology
Herpesviridae Infections / immunology
Herpesviridae Infections / veterinary
Immunity, Innate / genetics
Interferon Regulatory Factor-3 / genetics
Interferon Regulatory Factor-3 / immunology
Interferon Regulatory Factor-3 / metabolism
Interferon Type I / genetics
Interferon Type I / immunology
Interferon Type I / metabolism
Protein Serine-Threonine Kinases* / genetics
Protein Serine-Threonine Kinases* / immunology
Protein Serine-Threonine Kinases* / metabolism
Rhabdoviridae Infections* / immunology
Rhabdoviridae Infections* / veterinary
Rhabdoviridae* / physiology
Zebrafish Proteins

Substances

Irf3 protein, zebrafish

Supplementary concepts

Carp sprivivirus
Cyprinid herpesvirus 3