Defining influences on packaging and reassortment of the segmented reovirus genome

Viruses with multi-segmented genomes are unique in their capacity to readily exchange large amounts of genetic information via a process known as reassortment. Reassortment requires a considerable amount of genetic conservation on the part of parent viruses to successfully form viable reassortant progeny. As such, disruption of critical RNA and protein interactions, known as segment mismatch, is a major determinant of reassortment frequency. However, prior to this Dissertation, little was known about whether there are influences on the ability of viruses to reassort genome segments outside of segment mismatch. Furthermore, many viruses, including reovirus, package their multi-segmented genomes through a number of cis- and trans-segment interactions. In this Dissertation, I provide support for highly-specific viral genome packaging for some reovirus particles, while other particles package a number of host RNAs that exhibit structural similarity to reovirus mRNAs, highlighting the importance of structural determinants of reovirus packaging. Furthermore, I demonstrate that despite compartmentalizing replication and packaging, coinfecting reoviruses readily reassort genome segments, and replication dynamics play a critical role in determining the frequency of reassortment. Collectively, the work presented in this dissertation advances the understanding of how viruses package their multi-segmented genomes, and how they coordinate replication processes to allow for reassortment in the context of multiple infection. More broadly, this may help to elucidate the determinants and likelihood of natural reassortment events.