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dc.contributor.authorDlugolenski, Daniel Aaron
dc.date.accessioned2016-04-21T04:30:18Z
dc.date.available2016-04-21T04:30:18Z
dc.date.issued2015-12
dc.identifier.otherdlugolenski_daniel_a_201512_phd
dc.identifier.urihttp://purl.galileo.usg.edu/uga_etd/dlugolenski_daniel_a_201512_phd
dc.identifier.urihttp://hdl.handle.net/10724/35147
dc.description.abstractThe segmented genome of Influenza A viruses (IAV) allows for genetic exchange resulting in evolutionary shift. The 2009 pandemic was a result of a triple reassortment virus from avian, swine, and human origin which emerged from swine. Swine represent a mixing vessel for IAV supporting the replication of multiple lineages. Here, we investigated the role of the triple reassortment internal gene (TRIG) cassette in mediating species specific reassortment in swine with preferential reassortment of the glycoprotein genes hemagglutinin and neuraminidase. We also establish that Petrous Alecto kidney epithelial cells are permissive to infection with human and avian strains of IAV while supporting co-infection resulting in the generation of novel IAVs. Immediately after the introduction of the 2009 influenza virus pandemic, reverse zoonosis occurred in swine resulting in continued circulation of the pandemic H1N1 virus in swine. Continued circulation allowed for reassortment to occur resulting in the circulation of novel swine influenza viruses with altered pathogenic phenotypes as that observed with the pH1N1. In 2012, H3N2 variant (H3N2v) viruses were identified in Iowa state fairs in people which resulted from zoonotic transmission from swine. H3N2v infection resulted in enhanced morbidity and mortality and morbidity with the inability to transmit from person to person. Therefore, we investigated the pathogenic potential of reassortant viruses developed between the 2009 pH1N1 virus and an endemic circulating strain of swine influenza. To this end, we identified that specific genetic constellations and individual genes derived from swine could significantly enhance the pathology and immunopathology in ferrets and mice respectively. We show that the swine NA and PA can drive acute lung injury post infection through up regulation of MIP-2 resulting in increased neutrophil recruitment promoting inflammation and tissue damage.
dc.languageeng
dc.publisheruga
dc.rightspublic
dc.subjectInfluenza
dc.subjectreassortment
dc.subjectpathogenicity
dc.subjectacute lung injury
dc.titleUnderstanding features contributing to species-specific influenza virus reassortment and identification of novel influenza A virus pathogenicity factors
dc.typeDissertation
dc.description.degreePhD
dc.description.departmentInfectious Diseases
dc.description.majorInfectious Diseases
dc.description.advisorRalph Tripp
dc.description.committeeRalph Tripp
dc.description.committeeS. Mark Tompkins
dc.description.committeeMark Jackwood
dc.description.committeeBiao He
dc.description.committeeDonald Harn


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