期刊
NATURE MICROBIOLOGY
卷 6, 期 7, 页码 932-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41564-021-00907-x
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资金
- National Key Research and Development Program of China [2016YFD0500204]
- National Natural Science Foundation of China [81960297]
IFI16 enhances IFN-I response to inhibit influenza virus replication through its direct binding to viral RNA to promote RIG-I activation and by upregulating RIG-I expression via recruiting RNA polymerase II and binding to the RIG-I promoter. Additionally, IFI16 binds to influenza viral RNA and RIG-I protein through specific domains, facilitating IAV-induced K63-linked polyubiquitination and RIG-I activation.
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. IFI16 enhances the type I IFN response to inhibit influenza virus replication by two mechanisms: it directly binds viral RNA to promote RIG-I activation and upregulates RIG-I expression via recruiting RNA polymerase II and binding to the RIG-I promoter.
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