Patzina Corinna, Botting Catherine H, García-Sastre Adolfo, Randall Richard E, Hale Benjamin G
Institute of Medical Virology, University of Zurich, Winterthurerstrasse 190, Zurich 8057, Switzerland.
Biomedical Sciences Research Complex, University of St. Andrews, St. Andrews, Fife, KY16 9ST, UK.
J Gen Virol. 2017 Sep;98(9):2267-2273. doi: 10.1099/jgv.0.000909. Epub 2017 Sep 4.
NS1 proteins of influenza A and B viruses share limited sequence homology, yet both are potent manipulators of host cell processes, particularly interferon (IFN) induction. Although many cellular partners are reported for A/NS1, only a few (e.g. PKR and ISG15) have been identified for B/NS1. Here, affinity-purification and mass spectrometry were used to expand the known host interactome of B/NS1. We identified 22 human proteins as new putative targets for B/NS1, validating several, including DHX9, ILF3, YBX1 and HNRNPC. Consistent with two RNA-binding domains in B/NS1, many of the identified factors bind RNA and some interact with B/NS1 in an RNA-dependent manner. Functional characterization of several B/NS1 interactors identified SNRNP200 as a potential positive regulator of host IFN responses, while ILF3 exhibited dual roles in both IFN induction and influenza B virus replication. These data provide a resource for future investigations into the mechanisms underpinning host cell modulation by influenza B virus NS1.
甲型和乙型流感病毒的NS1蛋白序列同源性有限，但二者都是宿主细胞进程的有力调控因子，尤其是在干扰素（IFN）诱导方面。尽管已报道了许多与A/NS1相互作用的细胞伙伴，但与B/NS1相互作用的细胞伙伴仅鉴定出少数几种（如PKR和ISG15）。在此，利用亲和纯化和质谱法扩展了已知的B/NS1宿主相互作用组。我们鉴定出22种人类蛋白作为B/NS1新的假定靶点，并验证了其中几种，包括DHX9、ILF3、YBX1和HNRNPC。与B/NS1中的两个RNA结合结构域一致，许多鉴定出的因子都能结合RNA，并且有些因子以RNA依赖的方式与B/NS1相互作用。对几种B/NS1相互作用蛋白的功能表征确定了SNRNP200是宿主IFN反应的潜在正调控因子，而ILF3在IFN诱导和乙型流感病毒复制中均发挥双重作用。这些数据为未来研究乙型流感病毒NS1调控宿主细胞的机制提供了资源。
