Proteins Involved in Orthopoxvirus Intracellular Egress

参与正痘病毒细胞内流出的蛋白质

• 批准号: 8066722
• 负责人: BRIAN M WARD
• 金额: $ 19.09万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8066722
• 关键词: Actins; Antiviral Agents; Attenuated Vaccines; Biological; Biological Assay; Biology; Cell membrane; Cells; Cytoplasm; DNA Viruses; Disease; Disease Outbreaks; Dominant-Negative Mutation; Epidemic; Expression Library; Family; Family member; GPA33 gene; Goals; Golgi Apparatus; Hela Cells; Human; Hybrids; Infection; Intracellular Transport; Kinesin; Lead; Light; Mediating; Membrane; Microscopic; Microtubules; Molecular; Molecular Motors; Monkeypox; Morphogenesis; Motor; Mutation; Myosin Type V; Orthopoxvirus; Play; Poxviridae; Poxviridae Infections; Production; Proteins; Recombinant Vaccines; Reporting; Role; Site; Smallpox; Smallpox Vaccine; Smallpox Viruses; System; Systemic infection; Testing; Thick; Vaccinia virus; Viral; Viral Proteins; Virion; Virus; Work; Yeasts; base; epizootic; expression vector; in vivo; insight; member; monolayer; mutant; novel; prevent; protein function; protein protein interaction; public health relevance; trafficking; vector; virus envelope

DESCRIPTION (provided by applicant): Poxviruses include a large family of DNA viruses capable of infecting and causing disease in humans. While the most notorious member variola, the causative agent of smallpox, was eradicated from natural infection, there are still concerns about a clandestine release during a biological attack. In addition, monkeypox and other members of the family have raised concern about epizootic infections capable of causing epidemic. Poxviruses produce two infectious forms, enveloped and unenveloped virions. While unenveloped virions make up the majority of their progeny, it is the enveloped form that is required for efficient cell-to-cell spread and infection. Envelopment occurs in the cytoplasm of infected cells and only 7 proteins encoded by the virus are known to be unique to the enveloped form. The long-term goal of this project is to understand how these 7 proteins coordinate the monumental task of creating and releasing an enveloped virion. The immediate goal is to understand the function of the protein encoded by F12L. Our Hypothesis is that F12 interacts with the actin motor myosin V to facilitate virion transport through the actin cortex for egress. Our specific aims are: 1) Test for functional domains of F12, 2) Characterization of the kinesin-A36-F12 interaction, 3) Screen for additional proteins that interact with F12 and MyoV. The results obtained will provide greater insight into the interaction poxviruses have with their host at a molecular level and give us a better understanding of poxvirus morphogenesis and egress. PUBLIC HEALTH RELEVANCE: Even though natural occurring smallpox was eradicated, concern for orthopoxviruses, ranging from a clandestine release of smallpox to outbreaks of epizootic infections such as monkeypox, still exist. Understanding the biology of poxviruses is still a priority not only for preventing epidemics but also for understanding basic mechanisms of biology. The results from this study will provide new insights into poxvirus infections, which will provide new targets for antivirals and treatments against their infections.

描述(申请人提供)：痘病毒包括一大类DNA病毒，能够感染人类并导致疾病。虽然最臭名昭著的天花成员天花(天花的病原体)已从自然感染中根除，但仍有人担心在生物攻击期间秘密释放。此外，猴痘和其他家庭成员也提出了对可能导致流行病的流行性感染的担忧。痘病毒产生两种感染形式，有包膜的和无包膜的病毒粒子。虽然没有包膜的病毒粒子构成了它们后代的大部分，但它是有效的细胞间传播和感染所必需的包膜形式。包膜发生在感染细胞的细胞质中，目前已知只有7种由病毒编码的蛋白质是包膜形式所特有的。这个项目的长期目标是了解这7种蛋白质如何协调产生和释放被包裹的病毒粒子的艰巨任务。目前的目标是了解F12L编码的蛋白质的功能。我们的假设是，F12与肌动蛋白马达肌球蛋白V相互作用，促进病毒粒子通过肌动蛋白皮质转运出去。我们的具体目标是：1)测试F12的功能结构域，2)Kinesin-A36-F12相互作用的特征，3)筛选与F12和MyoV相互作用的额外蛋白质。所获得的结果将在分子水平上更好地了解痘病毒与宿主之间的相互作用，并使我们更好地理解痘病毒的形态发生和出口。 公共卫生相关性：尽管自然发生的天花已被根除，但对正痘病毒的担忧仍然存在，从秘密释放天花到爆发猴痘等流行性传染病。了解痘病毒的生物学仍然是一个优先事项，不仅对于预防流行病，而且对于了解生物学的基本机制。这项研究的结果将为研究痘病毒感染提供新的见解，这将为抗病毒药物和治疗其感染提供新的靶点。