Mount Sinai School of Medicine, New York, New York 10029, USA.
J Infect Dis. 2011 Nov;204 Suppl 3(Suppl 3):S904-10. doi: 10.1093/infdis/jir323.
The Ebola virus (EBOV) protein VP24 inhibits type I and II interferon (IFN) signaling by binding to NPI-1 subfamily karyopherin α (KPNA) nuclear import proteins, preventing their interaction with tyrosine-phosphorylated STAT1 (phospho-STAT1). This inhibits phospho-STAT1 nuclear import. A biochemical screen now identifies heterogeneous nuclear ribonuclear protein complex C1/C2 (hnRNP C1/C2) nuclear import as an additional target of VP24. Co-immunoprecipitation studies demonstrate that hnRNP C1/C2 interacts with multiple KPNA family members, including KPNA1. Interaction with hnRNP C1/C2 occurs through the same KPNA1 C-terminal region (amino acids 424-457) that binds VP24 and phospho-STAT1. The ability of hnRNP C1/C2 to bind KPNA1 is diminished in the presence of VP24, and cells transiently expressing VP24 redistribute hnRNP C1/C2 from the nucleus to the cytoplasm. These data further define the mechanism of hnRNP C1/C2 nuclear import and demonstrate that the impact of EBOV VP24 on nuclear import extends beyond STAT1.
埃博拉病毒（EBOV）蛋白 VP24 通过与核输入蛋白 NPI-1 亚家族 karyopherin α（KPNA）结合，抑制 I 型和 II 型干扰素（IFN）信号通路，从而阻止它们与酪氨酸磷酸化 STAT1（phospho-STAT1）相互作用。这抑制了 phospho-STAT1 的核内输入。目前的生化筛选确定了异质核核糖核蛋白复合物 C1/C2（hnRNP C1/C2）核内输入是 VP24 的另一个靶标。免疫共沉淀研究表明，hnRNP C1/C2 与多个 KPNA 家族成员相互作用，包括 KPNA1。hnRNP C1/C2 与 KPNA1 的相互作用发生在与 VP24 和 phospho-STAT1 结合的相同 KPNA1 C 末端区域（氨基酸 424-457）。在 VP24 存在的情况下，hnRNP C1/C2 与 KPNA1 的结合能力降低，并且瞬时表达 VP24 的细胞将 hnRNP C1/C2 从核内重新分布到细胞质中。这些数据进一步定义了 hnRNP C1/C2 核内输入的机制，并表明 EBOV VP24 对核内输入的影响超出了 STAT1。
