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Vet Microbiol
. 2025 Aug 29:309:110702.
doi: 10.1016/j.vetmic.2025.110702. Online ahead of print. Transcriptome profiling reveals a peculiarity of host immune responses to PA-X protein of H9N2 influenza A virus
Jinsen Wu 1 , Zhimin Wan 1 , Hongxia Shao 1 , Kun Qian 1 , Jiangqiang Ye 1 , Aijian Qin 2
Affiliations
H9N2 avian influenza virus is widely prevalent among poultry populations around the word. PA-X protein of the virus is recognized as pivotal for pathogenicity and replication. However, the molecular mechanisms which remodel host immunity is unclear. In this study, we investigated the function of PA-X in H9N2 using a mutant PA-X recombinant virus（ΔPAX-rH9N2）which did not express PA-X protein. We found PA-X protein significantly impaired viral replication in chicken embryos and mammalian cell lines. Transcriptomic analysis further indicated that PA-X extensively modulates host responses. Through stringent screening, we identified 326 differentially expressed genes and found enriched in immune pathways, membrane systems, and metabolic processes. RT-qPCR confirmed that ΔPAX-rH9N2 infection suppressed the expression of inflammatory cytokines and inhibited type I interferon production via the TLR3-IRF7-IFNβ axis. Moreover, ΔPAX-rH9N2 impaired NLRP3 inflammasome activation, leading to reduced Caspase-1 cleavage, decreased GSDMD processing, and attenuated IL-1β maturation. Collectively, these findings demonstrate that the PA-X protein in H9N2 influenza A virus serves to balance host immune responses.
Keywords: H9N2; IL-1β; PA-X; inflammatory cytokines; transcriptomic; type I interferon.
. 2025 Aug 29:309:110702.
doi: 10.1016/j.vetmic.2025.110702. Online ahead of print. Transcriptome profiling reveals a peculiarity of host immune responses to PA-X protein of H9N2 influenza A virus
Jinsen Wu 1 , Zhimin Wan 1 , Hongxia Shao 1 , Kun Qian 1 , Jiangqiang Ye 1 , Aijian Qin 2
Affiliations
- PMID: 40897025
- DOI: 10.1016/j.vetmic.2025.110702
H9N2 avian influenza virus is widely prevalent among poultry populations around the word. PA-X protein of the virus is recognized as pivotal for pathogenicity and replication. However, the molecular mechanisms which remodel host immunity is unclear. In this study, we investigated the function of PA-X in H9N2 using a mutant PA-X recombinant virus（ΔPAX-rH9N2）which did not express PA-X protein. We found PA-X protein significantly impaired viral replication in chicken embryos and mammalian cell lines. Transcriptomic analysis further indicated that PA-X extensively modulates host responses. Through stringent screening, we identified 326 differentially expressed genes and found enriched in immune pathways, membrane systems, and metabolic processes. RT-qPCR confirmed that ΔPAX-rH9N2 infection suppressed the expression of inflammatory cytokines and inhibited type I interferon production via the TLR3-IRF7-IFNβ axis. Moreover, ΔPAX-rH9N2 impaired NLRP3 inflammasome activation, leading to reduced Caspase-1 cleavage, decreased GSDMD processing, and attenuated IL-1β maturation. Collectively, these findings demonstrate that the PA-X protein in H9N2 influenza A virus serves to balance host immune responses.
Keywords: H9N2; IL-1β; PA-X; inflammatory cytokines; transcriptomic; type I interferon.