1. Academic Validation
  2. IFI16 directly senses viral RNA and enhances RIG-I transcription and activation to restrict influenza virus infection

IFI16 directly senses viral RNA and enhances RIG-I transcription and activation to restrict influenza virus infection

  • Nat Microbiol. 2021 Jul;6(7):932-945. doi: 10.1038/s41564-021-00907-x.
Zhimin Jiang  # 1 Fanhua Wei  # 2 Yuying Zhang 3 Tong Wang 1 Weihua Gao 1 Shufang Yu 4 Honglei Sun 1 Juan Pu 1 Yipeng Sun 1 Mingyang Wang 1 Qi Tong 1 Chengjiang Gao 5 Kin-Chow Chang 6 Jinhua Liu 7
Affiliations

Affiliations

  • 1 Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.
  • 2 College of Agriculture, Ningxia University, Yinchuan, China. weifanhua999@163.com.
  • 3 School of Biological Science and Technology, University of Jinan, Jinan, China.
  • 4 College of Agriculture, Ningxia University, Yinchuan, China.
  • 5 Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, China.
  • 6 School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Sutton Bonington, UK.
  • 7 Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China. ljh@cau.edu.cn.
  • # Contributed equally.
Abstract

The retinoic acid-inducible gene I (RIG-I) receptor senses cytoplasmic viral RNA and activates type I interferons (IFN-I) and downstream Antiviral immune responses. How RIG-I binds to viral RNA and how its activation is regulated remains unclear. Here, using IFI16 knockout cells and p204-deficient mice, we demonstrate that the DNA sensor IFI16 enhances IFN-I production to inhibit influenza A virus (IAV) replication. IFI16 positively upregulates RIG-I transcription through direct binding to and recruitment of RNA polymerase II to the RIG-I promoter. IFI16 also binds to influenza viral RNA via its HINa domain and to RIG-I protein with its PYRIN domain, thus promoting IAV-induced K63-linked polyubiquitination and RIG-I activation. Our work demonstrates that IFI16 is a positive regulator of RIG-I signalling during Influenza Virus infection, highlighting its role in the RIG-I-like-receptor-mediated innate immune response to IAV and other RNA viruses, and suggesting its possible exploitation to modulate the Antiviral response.

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