Analysis of novel functions and interaction partners of the influenza A virus PB1-F2 protein

流感病毒感染仍然是全世界人类和动物健康的一个主要负担。虽然这些病毒已被广泛研究，但其致病性的分子基础仍未完全了解。2001年发现了一种具有促进细胞凋亡特征的新型流感病毒蛋白PB1-F2。最近的研究清楚地表明，该蛋白在体内是一个重要的致病因子，但其功能的分子基础尚未阐明。虽然迄今为止对PB1- f2的功能研究仅限于促凋亡特征，但我们能够确定该蛋白的全新作用：PB1- f2直接与PB1蛋白结合，从而改变感染细胞中聚合酶蛋白的定位，导致PB1- f2敲除病毒的小斑块表型。除了这个将在项目中进一步研究的发现之外，我们已经在酵母的两个杂交实验中发现了新的细胞相互作用伙伴，这表明PB1-F2作为先天细胞防御的拮抗剂的作用。我们将进一步研究PB1-F2生物学的这些全新方面，以阐明其详细的分子机制及其与病毒致病性的相关性。

Influenza virus infections are still a major burden to human and animal health worldwide. Although these viruses have been extensively studied, the molecular basis of pathogenicity is still not fully understood yet. In 2001 a novel influenza virus protein with apoptosis promoting features, PB1-F2, has been identified. Recent work clearly demonstrated that the protein is an important pathogenicity factor in vivo, however the molecular basis of this function has not been elucidated yet. While functional studies on PB1-F2 so far were exclusively restricted to the proapoptotic features we were able to identify a completely novel role of the protein: PB1-F2 directly binds to the PB1 protein and thereby alters localization of the polymerase protein in the infected cell, leading to a small plaque phenotype of PB1-F2 knock-out viruses. In addition to this finding that will be further investigated in the project, we have identified novel cellular interaction partners in yeast two hybrid assays that suggest a role of PB1-F2 as an antagonist of the innate cellular defense. These completely new aspects of PB1-F2 biology will be further studied to elucidate the detailed molecular mechanisms and the relevance for viral pathogenicity.