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

甲型流感病毒PB1-F2蛋白的新功能和相互作用伙伴分析

• 批准号: 100021526
• 负责人: Professor Dr. Stephan Ludwig
• 金额: --
• 依托单位: Abteilung für Molekulare Virologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/100021526?language=en
• 关键词: Analysis; novel; functions; interaction; partners

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.

流感病毒感染仍然是世界范围内人类和动物健康的主要负担。虽然这些病毒已经得到了广泛的研究，但致病的分子基础仍不完全清楚。2001年，一种新的具有促凋亡功能的流感病毒蛋白PB1-F2被鉴定出来。最近的研究清楚地表明，该蛋白是体内一个重要的致病因子，但其作用的分子基础尚未阐明。虽然到目前为止对PB1-F2的功能研究仅限于促凋亡功能，但我们能够确定该蛋白的一个全新的作用：PB1-F2直接与PB1蛋白结合，从而改变聚合酶蛋白在感染细胞中的定位，导致PB1-F2敲除病毒的小斑块表型。除了将在该项目中进一步研究的这一发现外，我们还在酵母中确定了新的细胞相互作用伙伴。两种杂交试验表明，PB1-F2作为天然细胞防御的拮抗剂发挥了作用。这些全新的PB1-F2生物学方面将被进一步研究，以阐明详细的分子机制及其与病毒致病性的相关性。