Determinants of Rotavirus Polymerase Localization and Activity

dc.contributor.authorMcKell, Allison Overstreeten
dc.contributor.committeechairMcDonald, Sarahen
dc.contributor.committeememberFriedlander, Michael J.en
dc.contributor.committeememberYuan, Lijuanen
dc.contributor.committeememberMeng, Xiang-Jinen
dc.contributor.committeememberDermody, Terence S.en
dc.contributor.departmentVeterinary Medicineen
dc.date.accessioned2017-09-20T08:00:51Zen
dc.date.available2017-09-20T08:00:51Zen
dc.date.issued2017-09-19en
dc.description.abstractRotavirus (RV) is a viral pathogen that causes severe, watery diarrhea and vomiting in the young of humans and other animals. RV infections result in over 200,000 pediatric deaths around the world each year, especially in developing nations. Within the infected host cell, RV forms inclusion bodies, called viroplasms, where many stages of viral replication occur. The RV polymerase, known as VP1, must localize to viroplasms during infection where it replicates the virus' RNA genome. The work described in this dissertation focused on identifying region(s) of VP1 essential for its viroplasmic localization and its function as a polymerase. We found that a single amino acid change in a region of the polymerase called the N-terminal domain negatively impacted its capacity to localize to viroplasms during infection as well as its enzymatic activity in a test tube. Follow up studies using VP1 proteins from divergent strains and a mutant containing only the N-terminal domain of VP1 provided more insight into polymerase localization determinants. In total, our work suggests that the VP1 N-terminal domain plays an important role in localizing the polymerase to viroplasms via interactions with other viral proteins and supporting its function as a polymerase.en
dc.description.degreePh. D.en
dc.format.mediumETDen
dc.identifier.othervt_gsexam:12663en
dc.identifier.urihttp://hdl.handle.net/10919/79145en
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectrotavirusen
dc.subjectpolymeraseen
dc.subjectlocalizationen
dc.subjectenzymatic activityen
dc.subjectconfocal microscopyen
dc.titleDeterminants of Rotavirus Polymerase Localization and Activityen
dc.typeDissertationen
thesis.degree.disciplineBiomedical and Veterinary Sciencesen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.leveldoctoralen
thesis.degree.namePh. D.en
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