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

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Title: Investigations into the viral molecular determinants of lethality of Punta Toro virus (Bunyaviridae, phlebovirus) in the Syrian hamster.
Author: Lucy Ann Perrone
Abstract: Punta 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 .
URI: http : / /hdl .handle .net /2152 .3 /238
Date: 2006-04-21

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Investigations into the viral molecular determinants of lethality of Punta Toro virus (Bunyaviridae, phlebovirus) in the Syrian hamster.. Doctoral dissertation, The University of Texas Medical Branch. Available electronically from http : / /hdl .handle .net /2152 .3 /238 .

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