Abstract：
Influenza A virus (IAV) continuously poses a considerable threat to global health through seasonal epidemics and recurring pandemics. IAV RNA-dependent RNA polymerases (FluPol) mediate the transcription of RNA and replication of the viral genome. Searching for targets that inhibit viral polymerase activity helps us develop better antiviral drugs. Here, we identified heterogeneous nuclear ribonucleoprotein A/B (hnRNPAB) as an anti-influenza host factor. hnRNPAB interacts with NP of IAV to inhibit the interaction between PB1 and NP, which is dependent on the 5-amino-acid peptide of the hnRNPAB C-terminal domain (aa 318-322). We further found that the 5-amino-acid peptide blocks the interaction between PB1 and NP to destroy the FluPol activity. In vivo studies demonstrate that hnRNPAB-deficient mice display higher viral burdens, enhanced cytokine production, and increased mortality after influenza infection. These data demonstrate that hnRNPAB perturbs FluPol complex conformation to inhibit IAV infection, providing insights into anti-influenza defense mechanisms.
摘要：
甲型流感病毒（IAV）通过季节性流行和反复流行对全球健康构成相当大的威胁。IAVRNA依赖性RNA聚合酶(FluPol)介导RNA的转录和病毒基因组的复制。寻找抑制病毒聚合酶活性的靶标有助于我们开发更好的抗病毒药物。这里,我们鉴定了异质核核糖核蛋白A/B(hnRNPAB)作为抗流感宿主因子.hnRNPAB与IAV的NP相互作用以抑制PB1与NP之间的相互作用，其依赖于hnRNPABC末端结构域的5-氨基酸肽(aa318-322)。我们进一步发现5-氨基酸肽阻断PB1和NP之间的相互作用以破坏FluPol活性。体内研究表明，hnRNPAB缺陷小鼠表现出更高的病毒负担，增强细胞因子的产生，流感感染后死亡率增加。这些数据表明hnRNPAB干扰FluPol复合物构象以抑制IAV感染，提供抗流感防御机制的见解。
