Mechanism of Superinfection Exclusion By An RNA Virus

智力优势：当细胞被一种病毒（原发病毒）感染时，对第二种病毒（继发病毒）的感染产生抵抗力，这被称为“超级感染排斥”（SIE）。当病毒属于相同或密切相关的类型时，就会出现这种现象，并且已经观察到病毒，其中一些是病原体，可以感染各种生物体，包括人类，动物和植物。SIE最初用于检测植物病毒的亲缘关系，后来发展成为一种保护措施。故意感染一种无害的病毒株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使用基于病毒的疫苗。因此，对SIE机制的基本理解将有许多实际应用。然而，尽管其意义重大，我们对其机制的了解仍然令人惊讶地不完整。柑橘tristeza病毒（CTV）是Closteroviridae家族的一员，是高等植物中最大和最复杂的正链RNA病毒。CTV是在整个生物体水平上研究SIE的一个很好的模型系统，因为已经分离出了许多具有独特遗传特征的分离株。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起作用，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研究蛋白质-蛋白质相互作用和单个病毒超结构表征的创新技术相结合。预计该项目将促进我们对病毒与宿主之间以及同一宿主中病毒变体之间相互作用的一般认识，并加深我们对CTV中SIE的具体理解。更广泛的影响：更好地了解病毒变体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、动物和植物病毒性疾病的影响。教育部分：研究者的实验室位于佛罗里达州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。该项目与当地高中（海恩斯市高中和奥本代尔高中）和当地社区大学（波尔克州立大学）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。研究结果将通过在主要的同行评议期刊上发表和在科学会议上发表来广泛传播。

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.