The Tradeoffs for a Viral Mutant with Enhanced Replication Speed

dc.contributor.advisorGammon, Don B.en
dc.contributor.committeeMemberOrchard, Robert C.en
dc.contributor.committeeMemberWinter, Sebastian E.en
dc.creatorLanahan, Matthew Roberten
dc.creator.orcid0000-0002-6061-9513
dc.date.accessioned2021-09-17T18:00:52Z
dc.date.available2021-09-17T18:00:52Z
dc.date.created2021-08
dc.date.issued2021-07-26
dc.date.submittedAugust 2021
dc.date.updated2021-09-17T18:00:53Z
dc.description.abstractRNA viruses exist as genetically heterogeneous populations due to high mutation rates and many of these mutations reduce fitness and/or replication speed. However, it is unknown whether mutations can increase replication speed of a virus already well adapted to replication in cultured cells. By sequentially passaging coxsackievirus B3 in cultured cells and collecting the very earliest progeny, we selected for increased replication speed. We found that a single mutation in a viral capsid protein, VP1-F106L, was sufficient for the fast-replication phenotype. Characterization of this mutant revealed quicker genome release during entry compared to wild-type virus, highlighting a previously unappreciated infection barrier. However, this mutation also reduced capsid stability in vitro and reduced replication and pathogenesis in mice. These results reveal a tradeoff between overall replication speed and fitness. Importantly, this approach -- selecting for the earliest viral progeny -- could be applied to a variety of viral systems and has the potential to reveal unanticipated inefficiencies in viral replication cycles.en
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc1268338260
dc.identifier.urihttps://hdl.handle.net/2152.5/9631
dc.language.isoenen
dc.subjectAdaptation, Biologicalen
dc.subjectBiological Evolutionen
dc.subjectCapsiden
dc.subjectCoxsackievirus Infectionsen
dc.subjectGenome, Viralen
dc.subjectRNA Virusesen
dc.subjectViral Core Proteinsen
dc.titleThe Tradeoffs for a Viral Mutant with Enhanced Replication Speeden
dc.typeThesisen
dc.type.materialtexten
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineMolecular Microbiologyen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

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