Role of a viral long non-coding RNA in virus superinfection exclusion

Superinfection exclusion (SIE) has been observed for viruses that infect humans, animals, and plants. The phenomenon occurs when cells carrying a virus become protected from a secondary infection by the same or closely related virus. SIE influences the pathogenesis and evolution of viral populations and could have a profound impact on treating viral infections. Despite its significance, our understanding of SIE is far from being complete. The elucidation of the mechanisms underlying this phenomenon will provide a foundation for the development of novel approaches to mitigate viral diseases of humans, animals, and agricultural crops. From the educational standpoint, this project will provide an excellent opportunity for new students to get up-close research experience and for training rising scientists. The research results will be broadly disseminated through publishing in the leading peer-reviewed journals and presentations at scientific meetings. This project aims to unravel the mechanism of SIE of citrus tristeza virus (CTV), the largest non-segmented RNA virus of plants. CTV represents a valuable model system due to numerous well-characterized virus strains as well as a possibility to study the SIE phenomenon at the whole organism level. The project builds on the observations indicating that SIE by CTV functions through a unique mechanism, which involves multiple virus-encoded factors. The investigators' preliminary data suggest that a viral long non-coding RNA could play a role in this phenomenon. The project will utilize advanced molecular biology, microscopy, biochemistry, and genetic tools to further our understanding of viral SIE, interactions between virus variants in a host, and, importantly, the roles of viral lncRNAs, which represent a largely understudied research area, in the SIE phenomenon and in virus-host interactions. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.