Mechanism of Superinfection Exclusion By An RNA Virus

University Of Florida, Gainesville FL

Investigators

Abstract

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.