Wang X, Lin L, Chen Z, Si W, Yan Y, Dong W, Jin Y,. Mutations at site 207 of influenza a virus NS1 protein switch its function in regulating RIG-I-like receptors mediated antiviral responses. Antiviral Res. 2023 May 23:105641
RIG-I-like receptors (RLRs), retinoic acid inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5), are pattern recognition receptors through which cells initially sense pathogenic RNA and trigger interferon (IFN) signaling. Herein, we report that interferon induced protein 35 (IFI35) activates the ring finger protein 125 (RNF125)-UbcH5c-dependent degradation of RLRs and represses the recognition by RIG-I and MDA5 of viral RNA to inhibit innate immunity. Furthermore, IFI35 binds selectively to different subtypes of influenza A virus (IAV) nonstructural protein 1 (NS1) with asparagine residue207 (N207). Functionally, the NS1(N207)-IFI35 interaction restores the activity of RLRs, and IAV with NS1(non-N207) showed high pathogenicity in mice. Big data analysis showed that the 21st century pandemic IAV are almost all characterized by NS1 protein with non-N207. Collectively, our data uncovered the mechanism of IFI35 restricting the activation of RLRs and provides a new drug target comprising the NS1 protein of different IAV subtypes.
See Also:
Latest articles in those days:
- The evolution, complexity, and diversity of swine influenza viruses in China: A hidden public health threat 18 hours ago
- MHC class II proteins mediate sialic acid independent entry of human and avian H2N2 influenza A viruses 18 hours ago
- Histopathologic Features and Viral Antigen Distribution of H5N1 Highly Pathogenic Avian Influenza Virus Clade 2.3.4.4b from the 2022–2023 Outbreak in Iowa Wild Birds 18 hours ago
- Detection and characterization of H5N1 HPAIV in environmental samples from a dairy farm 22 hours ago
- Genomic Characterization of Highly Pathogenic Avian Influenza A H5N1 Virus Newly Emerged in Dairy Cattle 22 hours ago
[Go Top] [Close Window]