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dc.contributor.advisorQiu, Jianming
dc.contributor.authorChen, Yun
dc.date.accessioned2010-10-03T14:10:30Z
dc.date.available2010-10-03T14:10:30Z
dc.date.issued2010-06-25
dc.date.submitted2010
dc.identifier.otherhttp://dissertations.umi.com/ku:10755
dc.identifier.urihttp://hdl.handle.net/1808/6778
dc.description.abstractThe studies to be presented are composed of two parts: 1) investigating the molecular mechanisms underlying cytopathic effects induced during infections of parvovirus B19 (B19V) and minute virus of canines (MVC); 2) identifying the role of EpoR signaling in supporting B19V replication in erythroid of progenitor cells. To the first part, we take advantage of a recently developed in vitro permissive B19V infection system, and demonstrate that the small nonstructural protein 11kDa of B19V is a novel pro-apoptotic protein, which plays a key role in inducing apoptosis during B19V infection of erythroid progenitor cells. Caspase-10 may serve as an initiator in apoptosis of both B19V-infected and 11kDa-expressing cells. In contrast, apoptotic cell death during MVC infection appears to be viral DNA replication-dependent rather than viral protein-induced. A mitochondrion-mediated intrinsic apoptosis pathway is identified. In addition, a G2/M arrest of cell cycle during MVC infection is caused by the viral genome. Results in the second part represent the first attempt to explore the role of Epo/EpoR/Jak2 signaling during B19V infection. It not only establishes a direct connection of the Epo/EpoR signaling with B19V DNA replication, but also proposes a candidate of ant-B19V drug. In addition, our findings promote a novel concept that the cellular microenvironment determines the exclusive tropism of B19V to erythroid progenitor cells, in addition to B19V receptor and co-receptors. Our work provides insights into virus-host interaction during both early and late stages of parvovirus infection. Exploration of the cytopathic effects induced during infection shows that distinct mechanisms can be employed effectively by parvoviruses from different genera. In addition, we have introduced a novel concept that a unique cellular microenvironment in erythroid progenitor cells is prerequisite to B19V DNA replication, and thus determines the permissiveness of B19V infection.
dc.format.extent167 pages
dc.language.isoen
dc.publisherUniversity of Kansas
dc.rightsThis item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
dc.subjectBiology
dc.subjectMicrobiology
dc.subjectMolecular biology
dc.subjectCell cycle
dc.subjectCell death
dc.subjectEpo/epor/jak2
dc.subjectHuman parvovirus b19
dc.subjectParvovirus
dc.subjectTropism
dc.titleMolecular Mechanism of Parvovirus Infection
dc.typeDissertation
dc.contributor.cmtememberFontes, Joseph
dc.contributor.cmtememberLutkenhaus, Joe
dc.contributor.cmtememberStephens, Edward
dc.contributor.cmtememberVines, Charlotte
dc.contributor.cmtememberYankee, Thomas
dc.thesis.degreeDisciplineMicrobiology, Molecular Genetics & Immunology
dc.thesis.degreeLevelPh.D.
kusw.oastatusna
kusw.oapolicyThis item does not meet KU Open Access policy criteria.
dc.rights.accessrightsopenAccess


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