Proteins Involved in Orthopoxvirus Intracellular Egress

描述（由申请人提供）：痘病毒包括一个能够感染和引起人类疾病的DNA病毒大家族。虽然最臭名昭著的天花病毒，天花的病原体，已经从自然感染中被根除，但人们仍然担心在生物攻击期间秘密释放。此外，猴痘和其他家族成员引起了人们对能够引起流行病的动物传染病的关注。痘病毒产生两种感染形式，包膜病毒粒子和无包膜病毒粒子。虽然无包膜病毒粒子占其后代的大多数，但包膜形式是有效的细胞间传播和感染所必需的。包膜发生在受感染细胞的细胞质中，已知只有7种病毒编码的蛋白质是包膜形式所特有的。该项目的长期目标是了解这7种蛋白质如何协调创造和释放包膜病毒粒子的艰巨任务。当前的目标是了解由F12L编码的蛋白质的功能。我们的假设是F12与肌动蛋白运动肌凝蛋白V相互作用，促进病毒粒子通过肌动蛋白皮层运输并出口。我们的具体目标是：1)测试F12的功能域，2)表征激酶- a36 -F12相互作用，3)筛选与F12和MyoV相互作用的其他蛋白。所获得的结果将在分子水平上更深入地了解痘病毒与宿主的相互作用，并使我们更好地了解痘病毒的形态发生和输出。

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.