Factors That Influence Mammalian Enteric Virus Infection




Aguilera, Elizabeth Renata

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RNA viruses are a common cause of emerging diseases due to their vast genetic diversity. This diversity is largely attributed to mutations generated by the error-prone viral RNA-dependent RNA polymerase during replication. Despite the ability to acquire mutations beneficial to the virus, most mutations are deleterious and reduce viral fitness. This poses an obstacle for RNA viruses to successfully infect the host. In addition, a subset of RNA viruses are also enteric pathogens. In particular, these viruses must navigate several environments for transmission and subsequent infection through the fecal-oral route. In this work, I used poliovirus, an enteric RNA virus from the Picornaviridae family, as a model system to study mechanisms of RNA virus co-infection and how bacteria influence picornavirus infection. Recent studies determined several modes of RNA virus transmission exist outside of canonical pathways, including en bloc transmission of multiple viruses into a single cell via bacteria or host-derived membrane vesicles. Co-infection of RNA viruses is important since it can enhance viral fitness. I determined that multiple polioviruses are found within a single plaque even at low multiplicity of infection. I also showed that poliovirus stocks contain virion aggregates and that aggregates induce co-infection. Furthermore, I found that co-infection frequency was increased when polioviruses were heavily mutagenized. This work suggests that co-infection can contribute to plaque formation and that co-infection may assist plaque formation in situations with high genomic damage. This work contributes to mechanisms that influence co-infection of RNA viruses and potentially drive viral evolution. Infection by members of the Picornaviridae family can cause respiratory, cardiac, gastrointestinal, and neurological disease. These and other viruses encounter various bacteria within the host and in the environment. Despite these close encounters, the effects of bacteria on picornaviruses is not completely understood. Previous work determined that poliovirus has enhanced virion stability when exposed to bacteria or bacterial polysaccharides. Therefore, I investigated whether bacteria broadly enhance stability of picornaviruses from three different genera: Enterovirus (PV and coxsackievirus B3 (CVB3)), Kobuvirus (Aichi virus) and Cardiovirus (Mengo virus). I determined that specific bacterial strains enhance thermal stability of subset of viruses, while others were stable in the absence of bacteria. Additionally, I determined that bacteria can stabilize the entire picornavirus panel when individually exposed to bleach. These effects are likely mediated through direct interactions with bacteria since viruses bound to bacteria in vitro. Overall, this work reveals shared and distinct effects of bacteria on a panel of picornaviruses with implications on viral transmission.

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