PA-X is a fusion protein of influenza virus which plays a crucial role in modulating influenza virus-induced host innate immune response and subsequent pathogenicity. However, the potential mechanism of PA-X regulation of the host innate immune response remains largely unknown. It is well known that NF-κB signal pathway is crucial for the immediate early step of immune responses activation, while the specific role of PA-X in NF-κB transcriptional activity is totally unknown. In this study, we initially showed that PA-X inhibits NF-κB transcription that stimulated by poly(I:C). We then further determined that the inhibitory effect on NF-κB activation mediated by PA-X was characterized by restricting NF-κB p65 nuclear translocation and nuclear NF-κB p65 activity but not by impeding the phosphorylation of NF-κB p65. Correspondingly, PA-X decreases the amount of NF-κB signaling pathway-associated genes, including TNF-α, Nos2, IL-6 and IL-2. Moreover, PA-X also suppresses both the mRNA and protein expression level of IFN-β, suggesting the direct contribution of PA-X to the inhibition of NF-κB-regulated IFN-β expression. Together, our study sheds light on the potential molecular mechanisms underlying the regulation of host NF-κB activity by PA-X and also identifies a novel functional role for PA-X in counteracting the host innate immune response. However, further exploration of the more elaborate mechanism of PA-X-mediated inhibition of NF-κB activity and the associated signaling pathway may help to elucidate its precise mechanism of evading and subverting the host immune response.

PA-X是流感病毒的融合蛋白，在调节流感病毒诱导的宿主先天免疫应答和随后的致病性中起关键作用。但是，PA-X调控宿主先天性免疫反应的潜在机制仍然未知。众所周知，NF-κB信号通路对于免疫应答激活的早期阶段至关重要，而PA-X在NF-κB转录活性中的具体作用是完全未知的。在这项研究中，我们最初显示了PA-X抑制由poly（I：C）刺激的NF-κB转录。然后我们进一步确定，PA-X介导的对NF-κB活化的抑制作用是通过限制NF-κBp65核转运和核NF-κBp65活性来表征的，而不是通过阻止NF-κBp65的磷酸化来表征的。相应地，PA-X减少了NF-κB信号通路相关基因的数量，包括TNF-α，Nos2，IL-6和IL-2。此外，PA-X还抑制IFN-β的mRNA和蛋白表达水平，表明PA-X对抑制NF-κB调节的IFN-β表达的直接贡献。总之，我们的研究揭示了PA-X调节宿主NF-κB活性的潜在分子机制，并且还确定了PA-X在抵消宿主固有免疫反应中的新功能。但是，对PA-X介导的NF-κB活性抑制及其相关信号通路的更详尽机制的进一步探索可能有助于阐明其逃避和破坏宿主免疫反应的确切机制。此外，PA-X还抑制IFN-β的mRNA和蛋白表达水平，表明PA-X对抑制NF-κB调节的IFN-β表达的直接贡献。总之，我们的研究揭示了PA-X调节宿主NF-κB活性的潜在分子机制，并且还确定了PA-X在抵消宿主固有免疫反应中的新功能。然而，对PA-X介导的NF-κB活性抑制及其相关信号通路的更详尽机制的进一步探索可能有助于阐明其逃避和破坏宿主免疫反应的确切机制。此外，PA-X还抑制IFN-β的mRNA和蛋白表达水平，表明PA-X对抑制NF-κB调节的IFN-β表达的直接贡献。总之，我们的研究揭示了PA-X调节宿主NF-κB活性的潜在分子机制，并且还确定了PA-X在抵消宿主固有免疫反应中的新功能。但是，对PA-X介导的NF-κB活性抑制及其相关信号通路的更详尽机制的进一步探索可能有助于阐明其逃避和破坏宿主免疫反应的确切机制。我们的研究揭示了PA-X调节宿主NF-κB活性的潜在分子机制，并鉴定了PA-X在抵消宿主固有免疫应答中的新功能。但是，对PA-X介导的NF-κB活性抑制及其相关信号通路的更详尽机制的进一步探索可能有助于阐明其逃避和破坏宿主免疫反应的确切机制。我们的研究揭示了PA-X调节宿主NF-κB活性的潜在分子机制，并鉴定了PA-X在抵消宿主固有免疫应答中的新功能。但是，对PA-X介导的NF-κB活性抑制及其相关信号通路的更详尽机制的进一步探索可能有助于阐明其逃避和破坏宿主免疫反应的确切机制。