Xue Ruixue, Bao Danqi, Ma Tianxin, Niu Shiqi, Wu Zihua, Lv Xuehua, Zhang Yunxiang, Xu Guanlong, Yan Dawei, Zhang Zhifei, Pan Xue, Yan Minghao, Teng Qiaoyang, Yuan Chunxiu, Li Zejun, Liu Qinfang
Shanghai Veterinary Research Institute, 518 Ziyue Road, Minhang District, Shanghai 200241, China.
Shandong Provincial Center for Animal Disease Control and Prevention (Shandong Provincial Center for Zoonoses Epidemiology Investigation and Surveillance), 4566 Tangye West Road, Licheng District, Jinan 250100, China.
Microorganisms. 2024 Dec 26;13(1):24. doi: 10.3390/microorganisms13010024.
During the life cycle of the influenza virus, viral RNPs (vRNPs) are transported to the nucleus for replication. Given that a large number of progeny viral RNA occupies the nucleus, whether there is any host protein located in the nucleus that recognizes the viral RNA and inhibits the viral replication remains largely unknown. In this study, to explore the role of hnRNPH1 in influenza virus infection, we knocked down and over-expressed the hnRNPH1 proteins in 293T cells, then infected the cells with the influenza virus. The results showed that the host hnRNPH1 inhibits the replication of H1N1 and H9N2 influenza viruses by restraining the polymerase activity of viruses. hnRNPH1 contains two RNA recognition motifs (RRM1) and RRM2. Further studies indicated that hnRNPH1 specifically binds to the viral RNA of the PB1, PA, and NP genes. Mutation of the key residues tryptophan and tyrosine in RRM1 and RRM2 abolished the binding affinity to viral RNA and the suppression of polymerase activity of the influenza virus. All the results suggested that hnRNPH1 suppresses polymerase activity and replication of the influenza virus by binding viral RNA.
在流感病毒的生命周期中，病毒核糖核蛋白（vRNPs）被转运到细胞核进行复制。鉴于大量子代病毒RNA占据细胞核，是否存在位于细胞核中的宿主蛋白识别病毒RNA并抑制病毒复制在很大程度上仍不清楚。在本研究中，为了探究异质性核糖核蛋白H1（hnRNPH1）在流感病毒感染中的作用，我们在293T细胞中敲低并过表达hnRNPH1蛋白，然后用流感病毒感染这些细胞。结果表明，宿主hnRNPH1通过抑制病毒的聚合酶活性来抑制H1N1和H9N2流感病毒的复制。hnRNPH1包含两个RNA识别基序（RRM1和RRM2）。进一步研究表明，hnRNPH1特异性结合PB1、PA和NP基因的病毒RNA。RRM1和RRM2中关键残基色氨酸和酪氨酸的突变消除了对病毒RNA的结合亲和力以及对流感病毒聚合酶活性的抑制作用。所有结果表明，hnRNPH1通过结合病毒RNA抑制流感病毒的聚合酶活性和复制。
