Investigations into the viral molecular determinants of lethality of Punta Toro virus (Bunyaviridae, phlebovirus) in the Syrian hamster.

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dc.contributor.advisorC.J. Peters, MDen_US
dc.contributor.committeeMemberStephen Higgs, PhDen_US
dc.contributor.committeeMemberShinji Makino,. DVM, PhDen_US
dc.contributor.committeeMemberChristopher Basler, PhDen_US
dc.contributor.committeeMemberAlan Barrett, PhDen_US
dc.creatorLucy Ann Perroneen_US
dc.date.accessioned2011-12-20T16:05:24Z
dc.date.available2009-06-09en_US
dc.date.available2011-12-20T16:05:24Z
dc.date.created2006-10-09en_US
dc.date.issued2006-04-21en_US
dc.description.abstractPunta Toro virus (PTV) is transmitted by sandlfies (Lutzomyia spp.) in Panama and Northern Columbia and causes an acute febrile illness in humans lasting 2-5 days. Human seroprevalence in regions within Panama have been reported up to 34% in the most easterly region of Darien however little is understood about the clinical spectrum of PTV induced illness, pathogenic mechanism and the viral ecology with respect to animal reservoirs and distribution. This dissertation addresses questions regarding viral genetics and their affect on virulence in the hamster model of Phlebovirus pathogenesis. This study reports that PTV strains isolated west of the Panama Canal are not lethal in hamsters and phylogenetic analysis of the coding sequences reveals the presence of genetic clades, indicating that PTV strains occupy distinct ecological niches within Panama. Studies reported here also reflect the absence of naturally occurring viral reassortants and in vitro reassortment experiments demonstrate segment segregation preferences amongst the RNA segments during replication and/or packaging. Viral reassortants were utilized to investigate the viral genome segment(s) responsible for hamster lethality, this study finds that the S segment can confer lethality independently. Further genetic investigation reveals that the NSs gene encoded by the S segment is a type 1 interferon antagonist. Taken together, this evidence indicates a mechanism of pathogenesis whereby early innate immune suppression by the viral NSs gene/protein in infected cells leads to uncontrolled viral replication that ultimately results in hamster death.en_US
dc.format.mediumelectronicen_US
dc.identifier.otheretd-10092006-111646en_US
dc.identifier.urihttp://hdl.handle.net/2152.3/238
dc.language.isoengen_US
dc.rightsCopyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works.en_US
dc.subjectreassortantsen_US
dc.subjectPunta Toro virusen_US
dc.subjectphlebovirusen_US
dc.subjectInterferon antagonismen_US
dc.subjecthamster lethalityen_US
dc.titleInvestigations into the viral molecular determinants of lethality of Punta Toro virus (Bunyaviridae, phlebovirus) in the Syrian hamster.en_US
dc.type.genredissertationen_US
dc.type.materialtexten_US
thesis.degree.departmentExperimental Pathologyen_US
thesis.degree.grantorThe University of Texas Medical Branchen_US
thesis.degree.levelDoctoralen_US
thesis.degree.namePhDen_US

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