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REVERSE GENETIC STRATEGIES TO INTERROGATE REASSORTMENT RESTRICTION AMONG GROUP A ROTAVIRUSES

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title
REVERSE GENETIC STRATEGIES TO INTERROGATE REASSORTMENT RESTRICTION AMONG GROUP A ROTAVIRUSES
author
Hall, Jessica Rae
abstract
Rotavirus (RV) is an 11-segmented, double-stranded RNA virus and gastrointestinal pathogen that infects a wide variety of mammalian and avian hosts. Because RV’s genome is segmented, when a host cell is co-infected by more than one strain of RV, homologous genome segments belonging to different strains could be exchanged, or reassort. In theory, this process could generate up to 211 possible genetically distinct progeny with genome segments derived from both co-infecting parental viruses. In reality, though, genomic analyses of clinically isolated RVs indicate that reassortment occurs less frequently than what would be predicted due to chance alone. It is hypothesized that reassortment is restricted by biochemical incompatibilities between two RV strains’ RNAs or proteins. This hypothesis could be tested using a reverse genetics approach. While a reverse genetics system for simian RV strain SA11 has been developed, is poses significant technical challenges to successful rescue of recombinant RVs. After achieving functionality of the existing reverse genetics system, it was used to generate a reassortant virus containing genome segment 11 (g11) from the genetically divergent human RV strain, Wa. The mono-reassortant RV exhibited a moderate replicative defect relative to wildtype SA11, demonstrating that not only can the existing reverse genetics system be used to rescue mono-reassortant RVs, but differences between SA11 and Wa g11 RNAs and proteins are important for viral replication in cell culture. Because human RVs are so genetically divergent from strain SA11, the development of a reverse genetics system for a Wa-like human RV would provide a critical platform upon which human RV biology could be studied. This work is significant because it furthers understanding of how genotypic differences between RV strains contribute to their biology.
contributor
McDonald, Sarah M (committee chair)
Lyles, Douglas S (committee member)
Pease, James B (committee member)
date
2019-09-05T08:35:23Z (accessioned)
2019-09-05T08:35:23Z (available)
2019 (issued)
degree
Biology (discipline)
identifier
http://hdl.handle.net/10339/94313 (uri)
language
en (iso)
publisher
Wake Forest University
type
Thesis

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