RUI: Characterizing Microvesicle-Mediated Rotavirus Transmission: Mechanisms and Evolutionary Impacts

This award supports research and educational activities to understand a newly discovered way that some viruses, including rotavirus, are transmitted between cells. Rotavirus is a major cause of severe diarrheal disease, leading to hundreds of thousands of preventable deaths in children under five each year, primarily in developing countries. Traditionally, scientists believed that viruses like rotavirus could only infect new cells as individual, free-floating particles. However, recent discoveries show that these viruses can be packaged together inside tiny membrane-bound sacs, called microvesicles, and transmitted as a group. This project investigates this collective infection process, which represents a major shift in understanding viral transmission, ecology, and evolution. By characterizing how microvesicles are used for transmission, this research could identify new targets for antiviral drugs, with significant global health implications. The project also has significant broader impacts, including the training of undergraduate and doctoral students. It will establish a new, research-based virology laboratory course at Queens College, filling a critical curriculum gap and providing students with training in advanced techniques such as microscopy and metagenomic sequencing. Furthermore, the project will engage local high school students in immersive laboratory experiences to inspire career exploration in STEM fields. Using rotavirus as a model system, this project will technically characterize microvesicle-mediated viral transmission and its evolutionary consequences. The research will first characterize the fundamental properties of this infection mode, including quantifying the number of viruses packaged per microvesicle, determining the proportion of defective viral particles, and comparing the productivity of microvesicle-borne infections to those initiated by free viruses. This work will also test the hypothesis that microvesicles preferentially package incomplete, non-infectious double-layered particles over fully infectious particles. Subsequently, the project will investigate the ecological and evolutionary outcomes by testing if microvesicle-carriage allows viruses to infect normally resistant cells, facilitates the co-packaging of genetically distinct viruses, and accelerates the rate of evolutionary adaptation through serial passage experiments. The resulting impacts on population genetic diversity will be measured using highly accurate Duplex Sequencing, providing novel insights into the evolutionary dynamics of collective viral transmission. 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.