2. Academic Validation
  3. 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.
PMID: 33986530 DOI: 10.1038/s41564-021-00907-x
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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