Proteins Involved in Orthopoxvirus Intracellular Egress

描述（由申请方提供）：痘病毒包括能够感染人类并引起人类疾病的DNA病毒大家族。虽然最臭名昭著的成员天花，天花的病原体，从自然感染中被根除，但仍然有人担心在生物攻击期间秘密释放。此外，猴痘和该家族的其他成员引起了人们对能够引起流行病的动物流行病感染的关注。痘病毒产生两种感染形式，包膜和无包膜病毒粒子。虽然无包膜病毒粒子构成其后代的大部分，但有效的细胞间传播和感染需要包膜形式。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建和释放包膜病毒体的艰巨任务。目前的目标是了解F12 L编码蛋白的功能。我们的假设是，F12与肌动蛋白运动肌球蛋白V相互作用，以促进病毒粒子运输通过肌动蛋白皮质的出口。我们的具体目标是：1）测试F12的功能结构域，2）表征驱动蛋白-A36-F12相互作用，3）筛选与F12和MyoV相互作用的其他蛋白。所获得的结果将提供更深入的了解痘病毒与其宿主在分子水平上的相互作用，并使我们更好地了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，从天花的秘密释放到动物流行病感染如猴痘的爆发，仍然存在。了解痘病毒的生物学仍然是一个优先事项，不仅是为了预防流行病，而且是为了了解生物学的基本机制。这项研究的结果将为痘病毒感染提供新的见解，这将为抗病毒药物和抗感染治疗提供新的靶点。

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.