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:
- Characterization of a reassortant H11N9 subtype avian influenza virus isolated from spot-billed duck in China 7 hours ago
- Impact of influenza virus infection on lung microbiome in adults with severe pneumonia 7 hours ago
- Influenza Defective Interfering Virus Promotes Multiciliated Cell Differentiation and Reduces the Inflammatory Response in Mice 24 hours ago
- Influenza-associated neurologic complications in children from an H3N2 outbreak in Shenzhen, China during COVID-19 lockdown 24 hours ago
- Rapid evolution of A(H5N1) influenza viruses after intercontinental spread to North America 3 days ago
[Go Top] [Close Window]