| dc.description.abstract | Extracellular vesicles (EVs) are membrane-bound structures that range in size and play a key role in cell-cell communication. Many viruses employ host cell-derived EVs as vehicles of egress. EV-mediated viral transport may be advantageous for viral infection by facilitating multiparticle infection and immune system defense evasion. I wanted to determine how reovirus is released from infected cells, and I wanted to further understand how the mode of reovirus egress influences downstream infection of recipient cells. I show that in two separate cell types, infectious units of two reovirus strains with distinct membrane disruption capacities egress both as free virus particles and associated with large and medium EVs, but not with small EVs. These medium-sized EVs measure, on average, 600-1000 nm in diameter, are resistant to mechanical disruption, and can withstand a variety of storage conditions. Furthermore, I show that medium EVs can protect reovirus particles from antibody neutralization and proteolysis in a cell type- and virus strain-dependent manner. This protection phenotype may be influenced by the capacity of the virus to induce cell death. Such neutralization protection potentially occurs in vivo, as I observe a trend towards reovirus protection by medium EVs harvested from infected mice. Additionally, EVs permit reovirus to be transported between cells in multiparticle infectious units. Finally, reovirus enhances the release of EVs of all sizes during infection. Overall, my work reveals mechanisms by which reovirus may escape immune system defenses and overcome cellular thresholds to infection, enhancing the likelihood of productive infection. These findings, which enhance our field’s current understanding of the effect of egress strategy on virus infection, may apply broadly to other viruses, including highly pathogenic viruses that are released and travel in association with EVs. Further insights into the mechanisms and effects of EV-mediated virus egress may help inform viral vaccination strategies and delivery of viral vectors. | |
