Molecular Mechanism of Parvovirus Infection

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Issue Date
2010-06-25Author
Chen, Yun
Publisher
University of Kansas
Format
167 pages
Type
Dissertation
Degree Level
Ph.D.
Discipline
Microbiology, Molecular Genetics & Immunology
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This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
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Show full item recordAbstract
The 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.
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