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

Jiang, Zhimin; Wei, Fanhua; Zhang, Yuying; Wang, Tong; Gao, Weihua; Yu, Shufang; Sun, Honglei; Pu, Juan; Sun, Yipeng; Wang, Mingyang; Tong, Qi; Gao, Chengjiang; Chang, Kin-Chow; Liu, Jinhua

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


Authors

Zhimin Jiang

Fanhua Wei

Yuying Zhang

Tong Wang

Weihua Gao

Shufang Yu

Honglei Sun

Juan Pu

Yipeng Sun

Mingyang Wang

Qi Tong

Chengjiang Gao

KIN-CHOW CHANG KIN-CHOW.CHANG@NOTTINGHAM.AC.UK
Professor of Veterinary Molecular Medicine

Jinhua Liu



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.

Citation

Jiang, Z., Wei, F., Zhang, Y., Wang, T., Gao, W., Yu, S., …Liu, J. (2021). IFI16 directly senses viral RNA and enhances RIG-I transcription and activation to restrict influenza virus infection. Nature Microbiology, 6, 932–945. https://doi.org/10.1038/s41564-021-00907-x

Journal Article Type Article
Acceptance Date Apr 6, 2021
Online Publication Date May 13, 2021
Publication Date May 13, 2021
Deposit Date May 18, 2021
Publicly Available Date Nov 14, 2021
Journal Nature Microbiology
Electronic ISSN 2058-5276
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 6
Pages 932–945
DOI https://doi.org/10.1038/s41564-021-00907-x
Keywords Immunology; Microbiology (medical); Applied Microbiology and Biotechnology; Genetics; Cell Biology; Microbiology
Public URL https://nottingham-repository.worktribe.com/output/5531000
Publisher URL https://www.nature.com/articles/s41564-021-00907-x

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