Mechanism of Superinfection Exclusion By An RNA Virus

智力优点：当被一种病毒（初级病毒）感染的细胞对第二种病毒（次级病毒）的感染产生抵抗力时，这被称为“超级感染排除”（SIE）。 当病毒属于相同或密切相关的类型时，这种现象就会发生，并且已经观察到病毒，其中一些是病原体，感染各种生物体，包括人类，动物和植物。SIE最初用于测试植物病毒的相关性，随后发展成为一种保护措施。人们发现，用一种无害的病毒株故意感染植物可以保护植物免受相关致病病毒的感染。在医学和兽医实践中，发现SIE降低了多组分疫苗的有效性，以及对持续感染的个体重复应用病毒疫苗的有效性。因此，对SIE机制的基本理解将具有许多实际应用。然而，尽管其意义重大，我们对该机制的了解仍然令人惊讶地不完整。柑橘衰退病毒（Citrus tristeza virus，CTV）是高等植物中最大、最复杂的正链RNA病毒，属于梭状病毒科（Closteroviridae）的一个成员。CTV代表了一个很好的模式系统，在整个生物体水平上研究SIE，因为许多具有独特的遗传特征的分离物已被分离。 该项目建立在观察的基础上，表明SIE在CTV中通过一种独特的机制运作，可能涉及CTV基因组编码新病毒蛋白的两个区域。 先进的遗传工具将与创新技术相结合，用于研究蛋白质-蛋白质相互作用和单个病毒的超微结构特征。预计该项目将推进我们对病毒与其宿主之间以及同一宿主中病毒变体之间相互作用的一般知识，并加深我们对CTV中SIE的具体理解。 更广泛的影响：更好地了解病毒变种如何相互作用和相互排斥，对于更全面地了解病毒种群的进化和新病毒的出现至关重要。阐明SIE的机制也将有助于开发新的基于病毒的治疗方法，以减少人类，动物和植物病毒疾病的影响。教育部分：研究人员的实验室位于佛罗里达中部的柑橘研究和教育中心，该地区几乎没有其他研究机构。PI与当地高中（海恩斯市和奥本代尔高中）和当地社区学院-波尔克州立学院建立了联系，以确定和招募学生，包括代表性不足的群体的成员，以重要和有意义的方式参与拟议的研究。这些努力将加强佛罗里达中部的研究和教育基础设施。研究结果将通过在领先的同行评审期刊上发表和在科学会议上发表而广泛传播。

Intellectual merit: When cells infected by one virus (the primary virus) become resistant to infection by a second virus (the secondary virus), this is called "Super-Infection Exclusion" (SIE). This phenomenon occurs when the viruses belong to the same or closely related types and has been observed for viruses, some of them pathogens, that infect various kinds of organisms, including humans, animals, and plants. SIE was initially used to test the relatedness of plant viruses and subsequently developed into a protective measure. Deliberate infection with a harmless viral strain was found to protect plants from infection by related pathogenic viruses. In medical and veterinary practice, SIE was found to diminish the effectiveness of multi-component vaccines, as well as of repeated applications of virus-based vaccines to individuals with persistent infections. Thus, fundamental understanding of the mechanism of SIE will have many practical applications. In spite of its significance, however, our knowledge of the mechanism remains surprisingly incomplete. This project aims to elucidate the mechanism of SIE in Citrus tristeza virus (CTV), a member of the Closteroviridae family, which includes the largest and most complex positive-strand RNA viruses of higher plants. CTV represents an excellent model system to study SIE at the whole organism level, because numerous isolates having distinctive genetic characteristics have been isolated. The project builds on observations suggesting that SIE operates by a unique mechanism in CTV, possibly involving two regions of the CTV genome coding for novel viral proteins. Advanced genetic tools will be combined with innovative techniques for studying protein-protein interactions and ultra-structural characterization of individual viruses. It is anticipated that the project will advance our general knowledge of the interactions between viruses and their hosts and between virus variants in the same host, as well as deepen our specific understanding of SIE in CTV. Broder impacts: Better understanding of how virus variants interact and exclude each other is crucial to more complete understanding of the evolution of virus populations and the emergence of new viruses. Elucidation of the mechanism(s) of SIE will also contribute to the development of novel virus-based therapeutics to reduce the effects of human, animal and plant viral diseases. Education component: The investigator's laboratory is located at the Citrus Research and Education Center in Central Florida, a region with few other research institutions. The PI has established connections with local high schools (Haines City and Auburndale High schools) and the local community college - Polk State College - to identify and recruit students, including members of under-represented groups, to participate in the proposed research in significant and meaningful ways. These efforts will enhance the infrastructure for research and education in Central Florida. The research results will be broadly disseminated via publishing in the leading peer-reviewed journals and presentations at scientific meetings.