tetano
Editor, Senior Moderator
Nat Microbiol
. 2021 May 13.
doi: 10.1038/s41564-021-00907-x. Online ahead of print.
IFI16 directly senses viral RNA and enhances RIG-I transcription and activation to restrict influenza virus infection
Zhimin Jiang[SUP] #[/SUP][SUP] 1 [/SUP], Fanhua Wei[SUP] #[/SUP][SUP] 2 [/SUP], Yuying Zhang[SUP] 3 [/SUP], Tong Wang[SUP] 1 [/SUP], Weihua Gao[SUP] 1 [/SUP], Shufang Yu[SUP] 4 [/SUP], Honglei Sun[SUP] 1 [/SUP], Juan Pu[SUP] 1 [/SUP], Yipeng Sun[SUP] 1 [/SUP], Mingyang Wang[SUP] 1 [/SUP], Qi Tong[SUP] 1 [/SUP], Chengjiang Gao[SUP] 5 [/SUP], Kin-Chow Chang[SUP] 6 [/SUP], Jinhua Liu[SUP] 7 [/SUP]
Affiliations
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.
. 2021 May 13.
doi: 10.1038/s41564-021-00907-x. Online ahead of print.
IFI16 directly senses viral RNA and enhances RIG-I transcription and activation to restrict influenza virus infection
Zhimin Jiang[SUP] #[/SUP][SUP] 1 [/SUP], Fanhua Wei[SUP] #[/SUP][SUP] 2 [/SUP], Yuying Zhang[SUP] 3 [/SUP], Tong Wang[SUP] 1 [/SUP], Weihua Gao[SUP] 1 [/SUP], Shufang Yu[SUP] 4 [/SUP], Honglei Sun[SUP] 1 [/SUP], Juan Pu[SUP] 1 [/SUP], Yipeng Sun[SUP] 1 [/SUP], Mingyang Wang[SUP] 1 [/SUP], Qi Tong[SUP] 1 [/SUP], Chengjiang Gao[SUP] 5 [/SUP], Kin-Chow Chang[SUP] 6 [/SUP], Jinhua Liu[SUP] 7 [/SUP]
Affiliations
- 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.