REASSORTMENT AND GENE SELECTION OF INFLUENZA VIRUSES IN THE FERRET MODEL AND POTENTIAL PLATFORMS FOR IN VIVO REVERSE GENETICS

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dc.contributor.advisorPerez, Daniel Ren_US
dc.contributor.authorAngel, Matthew Grayen_US
dc.contributor.departmentCell Biology & Molecular Geneticsen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.date.accessioned2014-06-24T06:06:29Z
dc.date.available2014-06-24T06:06:29Z
dc.date.issued2014en_US
dc.description.abstractInfluenza A virus is a highly infectious agent that cause seasonal epidemics affecting 5-15% of the world population with mild to severe illness and possibly death. While this pathogen represents a significant disease burden to the human population, it can also infect a wide range of animals including swine and land-based poultry, which are thought to serve as intermediate hosts between the human and natural wild aquatic bird reservoir. Here, two viruses, a swine-origin pandemic H1N1 and a seasonal human H3N2 are examined for segment fitness during co-infection of in vivo animal models. In three independent co-infections, reassortment between seasonal and pandemic viruses resulted in the selection of an H1N2 virus with a seasonal PB1 with an otherwise pandemic internal gene constellation. Selection for the seasonal PB1 and NA as well as the pandemic M segment was observed to occur rapidly during segment resolution. As pandemic M gene reassortant strains are being consistently identified in the field, studies were performed to identify the genetic determinants in pandemic M gene selection. Research here shows that both the M1 capsid protein and M2 ion channel from the pandemic virus are sufficient to drive the selection of the entire M segment. As swine represent an important intermediate host for the adaptation of potentially pandemic viruses, including pandemic M gene reassortant strains, alternative DNA and recombinant baculovirus-based platforms are investigated for their ability to generate influenza viruses from porcine polymerase I promoters and serve as potential vaccine candidates. Research here shows that influenza A virus can be rescued de novo using the porcine polymerase I promoter in an eight plasmid system. Furthermore, a single bacmid can be constructed that rescues influenza virus or baculovirus encoding the influenza reverse genetic system in mammalian tissue culture or Sf9 cells, respectively. These represent a new generation of species-tailored vaccine platforms.en_US
dc.identifier.urihttp://hdl.handle.net/1903/15307
dc.language.isoenen_US
dc.subject.pqcontrolledVirologyen_US
dc.subject.pqcontrolledBiologyen_US
dc.subject.pqcontrolledGeneticsen_US
dc.subject.pquncontrolledinfluenzaen_US
dc.subject.pquncontrolledM2en_US
dc.subject.pquncontrolledpandemicen_US
dc.subject.pquncontrolledreassortmenten_US
dc.subject.pquncontrolledreverse geneticsen_US
dc.subject.pquncontrolledRNA polymerase Ien_US
dc.titleREASSORTMENT AND GENE SELECTION OF INFLUENZA VIRUSES IN THE FERRET MODEL AND POTENTIAL PLATFORMS FOR IN VIVO REVERSE GENETICSen_US
dc.typeDissertationen_US

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