ArticlePLoS pathogens2023
The synergistic effect of residues 32T and 550L in the PA protein of H5 subtype avian influenza virus contributes to viral pathogenicity in mice.
Article in PLoS pathogens, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- Emerged N193S mutation of PA-X protein disabled the immunity of mucosal dendritic cells for regulating virulence of clade 2.3.4.4b H5 subtype virus.Emerging microbes & infections · 2026Article
- On the brink of emergence: an evolutionary approach to Influenza A virus H5N1 isolated from humans.Virus research · 2026Article
- SARS-CoV-2 nonstructural protein 3 remodels the phosphorylation of target proteins via protein-protein interactions.Microbiology spectrum · 2026Article
- Phylogenetic Analyses and Biological Characterization of H9N2 Avian Influenza Virus Isolated from Chickens in China from 2022 to 2023.Microorganisms · 2025Article
- PA and PA-X: two key proteins from segment 3 of the influenza viruses.Frontiers in cellular and infection microbiology · 2025Review
- Two amino acid residues in the N-terminal region of the polymerase acidic protein determine the virulence of Eurasian avian-like H1N1 swine influenza viruses in mice.Journal of virology · 2024Article
- E3 ligase RNF2 inhibits porcine circovirus type 3 replication by targeting its capsid protein for ubiquitination-dependent degradation.Journal of virology · 2024Article
- Triggering Degradation of Host Cellular Proteins for Robust Propagation of Influenza Viruses.International journal of molecular sciences · 2024Review
- Naturally occurring PAVirologica Sinica · 2024Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The avian influenza virus (AIV) PA protein contributes to viral replication and pathogenicity; however, its interaction with innate immunity is not well understood. Here, we report that the H5 subtype AIV PA protein strongly suppresses host antiviral defense by interacting with and degrading a key protein in interferon (IFN) signaling, Janus kinase 1 (JAK1). Specifically, the AIV PA protein catalyzes the K48-linked polyubiquitination and degradation of JAK1 at lysine residue 249. Importantly, the AIV PA protein harboring 32T/550L degrades both avian and mammalian JAK1, while the AIV PA protein with residues 32M/550I degrades avian JAK1 only. Furthermore, the residues 32T/550L in PA protein confer optimum polymerase activity and AIV growth in mammalian cells. Notably, the replication and virulence of the AIV PA T32M/L550I mutant are attenuated in infected mice. Collectively, these data reveal an interference role for H5 subtype AIV PA protein in host innate immunity, which can be targeted for the development of specific and effective anti-influenza therapeutics.
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