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  • 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.

Nature microbiology (2021-05-15)
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, 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.

MATERIALS
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Product Description

Roche
Fluorescein RNA Labeling Mix, solution, suitable for Northern blotting, suitable for Southern blotting, suitable for hybridization