Hale Benjamin G, Knebel Axel, Botting Catherine H, Galloway Caroline S, Precious Bernard L, Jackson David, Elliott Richard M, Randall Richard E
Centre for Biomolecular Sciences, University of St. Andrews, North Haugh, St. Andrews, Fife KY16 9ST, UK.
Virology. 2009 Jan 5;383(1):6-11. doi: 10.1016/j.virol.2008.10.002. Epub 2008 Nov 13.
Posttranslational modification of viral proteins by cellular enzymes is a feature of many virus replication strategies. Here, we report that during infection the multifunctional human influenza A virus NS1 protein is phosphorylated at threonine-215. Substitution of alanine for threonine at this position reduced early viral propagation, an effect apparently unrelated to NS1 antagonizing host interferon responses or activating phosphoinositide 3-kinase signaling. In vitro, a subset of cellular proline-directed kinases, including cyclin dependent kinases (CDKs) and extracellular signal-regulated kinases (ERKs), potently phosphorylated NS1 protein at threonine-215. Our data suggest that CDK/ERK-mediated phosphorylation of NS1 at threonine-215 is important for efficient virus replication.
细胞酶对病毒蛋白进行的翻译后修饰是许多病毒复制策略的一个特点。在此，我们报告在感染过程中，多功能的人类甲型流感病毒NS1蛋白在苏氨酸-215处被磷酸化。该位置的苏氨酸被丙氨酸取代会降低病毒早期传播，这种效应显然与NS1拮抗宿主干扰素反应或激活磷酸肌醇3-激酶信号无关。在体外，包括细胞周期蛋白依赖性激酶（CDK）和细胞外信号调节激酶（ERK）在内的一组细胞脯氨酸定向激酶能有效地将NS1蛋白在苏氨酸-215处磷酸化。我们的数据表明，CDK/ERK介导的NS1在苏氨酸-215处的磷酸化对病毒的有效复制很重要。
