Administrative Supplement to Promote Diversity, R00 GM088484-04

促进多样性的行政补充，R00 GM088484-04

• 批准号: 8718181
• 负责人: Andrew Mehle
• 金额: $ 1.06万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-07 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8718181
• 关键词: Administrative Supplement; Avian Influenza A Virus; Biochemical Genetics; Birds; Chromosome Mapping; Complex; DNA Sequence Rearrangement; Event; Foundations; Future; Gene Expression; Genome; Human; Infection; Influenza; Influenza A virus; Instruction; Integration Host Factors; Molecular; Nucleoproteins; Pathogenicity; Pathway interactions; Phosphorylation; Phosphorylation Site; Polymerase; Population; Process; Proteins; Regulation; Resolution; Structure; System; Therapeutic Intervention; Translations; Viral; Viral Proteins; Virus Replication; flu transmission; influenza outbreak; influenzavirus; insight; loss of function; prevent; protein function; transmission process; viral RNA

Protein function is dynamically controlled by post-translation events. A connmon regulatory mechanism is the phosphorylation and subsequent conformational rearrangement of target proteins. Viral proteins are often controlled by the same pathways that target proteins encoded by the host. The replication cycle of influenza A virus is influenced by host proteins and provides a unique system in which to study these processes. A major target of regulation is the influenza virus replication machinery containing viral RNA, nucleoprotein (NP), and the trimeric polymerase composed ofthe proteins PB1, PB2, and PA. The replication machinery controls the ordered transition from gene expression to genome replication that is essential for a productive infection. In addition, the viral polymerase is a key determinant in the host range of influenza virus and restricts the transmission of influenza virus from avian to human populations. The processes controlling the replication machinery and the interplay between the polymerase and the host are poorly understood. We propose an integrative approach using biochemical, genetic, and structural studies to determine the host proteins and molecular mechanisms that regulate the influenza replication machinery. Specifically, Aim 1 will identify sites of phosphorylation within viral proteins and examine the functional consequences of phosphorylation on virus replication and the determination of host range. Aim 2 will build on recent genetic mapping of interactions to produce high-resolution crystal structures that characterize in detail the protein interfaces of the replication complex. Finally, Aim 3 will exploit loss-of-function screens to identify cellular proteins that regulate the influenza polymerase and control transmission of influenza from birds to humans. These studies will provide crucial insight into the viral and host factors controlling influenza replication and will provide the foundation for rational strategies to treat and prevent future influenza outbreaks in humans.

蛋白质的功能受到翻译后事件的动态控制。一个共同的法规

项目成果

Fiat Luc: Bioluminescence Imaging Reveals In Vivo Viral Replication Dynamics.

• DOI: 10.1371/journal.ppat.1005081
• 发表时间: 2015-09
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Mehle A

Multi-Modal Imaging with a Toolbox of Influenza A Reporter Viruses.

具有流感的工具箱的多模式成像记者病毒。

• DOI: 10.3390/v7102873
• 发表时间: 2015-10-13
• 期刊: Viruses
• 作者: Tran V;Poole DS;Jeffery JJ;Sheahan TP;Creech D;Yevtodiyenko A;Peat AJ;Francis KP;You S;Mehle A
• 通讯作者: Mehle A

Unusual influenza A viruses in bats.

• DOI: 10.3390/v6093438
• 发表时间: 2014-09-17
• 期刊: Viruses
• 作者: Mehle A

The Avian Influenza Virus Polymerase Brings ANP32A Home to Roost.

禽流感病毒聚合酶使 ANP32A 归巢。

• DOI: 10.1016/j.chom.2016.01.013
• 发表时间: 2016
• 期刊: Cell host & microbe
• 影响因子: 30.3
• 作者: Mehle,Andrew