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dc.contributor.authorWilliams, Trevor Paul Emrysen_US
dc.date.accessioned2014-03-14T20:36:44Z
dc.date.available2014-03-14T20:36:44Z
dc.date.issued2001-05-01en_US
dc.identifier.otheretd-05142001-131550en_US
dc.identifier.urihttp://hdl.handle.net/10919/32735
dc.description.abstractHepatitis E virus (HEV) is the major cause of enterically transmitted non-A, non-B hepatitis in many developing countries, and is also endemic in many industrialized countries. Due to the lack of an effective cell culture system and a practical animal model, the mechanisms of HEV pathogenesis and replication are poorly understood. It has been speculated that HEV replicates in sites other than the liver. Since HEV is presumably fecal-orally transmitted it is unclear how the virus reaches the liver and extrahepatic replication could be a possible explanation. The recent identification of swine HEV from pigs affords us an opportunity to systematically study HEV replication in a swine model. We experimentally infected specific-pathogen-free (SPF) pigs with two strains of HEV: swine HEV and the US-2 strain of human HEV. Eighteen pigs (group 1) were each inoculated intravenously with swine HEV, nineteen pigs (group 2) with the US-2 strain of human HEV, and seventeen pigs (group 3) as uninoculated controls. To identify the potential extrahepatic sites of HEV replication using the swine model, two pigs from each group were necropsied at 3, 7, 14, 20, 27, and 55 days post inoculation (DPI). Thirteen different types of tissues and organs were collected from each necropsied animal. Reverse transcriptase PCR (RT-PCR) was used to detect the presence of positive strand HEV RNA in each tissue collected during necropsy at different DPIs. A negative strand-specific RT-PCR was standardized and used to detect the replicative, negative-strand of HEV RNA from tissues that tested positive for the positive strand RNA. As expected, positive strand HEV RNA was detected in almost every type of tissue at some time point during viremic period between 3 and 27 DPI. Positive-strand HEV RNA was still detectable in some tissues in the absence of serum HEV RNA from both swine and human HEV inoculated pigs. However, replicative, negative strand of HEV RNA was detected primarily in the small intestine, lymph nodes, colon, and liver. Our results demonstrate for the first time that HEV replicates in tissues other than the liver and that the gastrointestinal tract is also the target of virus infection. The data from this study may have important implications for HEV pathogenesis, xenotransplantation, and the development of an in vitro cell culture system for HEV.en_US
dc.publisherVirginia Techen_US
dc.relation.haspartFMTPEWHEVThesis.pdfen_US
dc.relation.haspartAdd.Fig.TPEWHEVThesis.pdfen_US
dc.relation.haspartTPEWHEVThesis.pdfen_US
dc.rightsI hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Virginia Tech or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report.en_US
dc.subjectRT-PCRen_US
dc.subjectxenotransplantationen_US
dc.subjectzoonosisen_US
dc.subjectnegative strand RNAen_US
dc.titleEvidence of Extrahepatic Sites of Replication of the Hepatitis E Virus in a Swine Modelen_US
dc.typeThesisen_US
dc.contributor.departmentBiomedical Sciences and Pathobiologyen_US
dc.description.degreeMaster of Scienceen_US
thesis.degree.nameMaster of Scienceen_US
thesis.degree.levelmastersen_US
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen_US
thesis.degree.disciplineBiomedical Sciences and Pathobiologyen_US
dc.contributor.committeechairMeng, Xiang-Jinen_US
dc.contributor.committeememberToth, Thomas E.en_US
dc.contributor.committeememberAvery, Roger J.en_US
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-05142001-131550/en_US
dc.date.sdate2001-05-14en_US
dc.date.rdate2004-05-14
dc.date.adate2001-05-14en_US


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