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Theses and Dissertations

A large deletion virus reveals the presence of previously uncharacterized vaccinia virus inhibitors of NF-kB signaling Open Access

Descriptions

Other title
Subject/Keyword
vaccinia
virus
NF-kB
inhibitors
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Fagan-Garcia, Katharine
Supervisor and department
Barry, Michele (Medical Microbiology and Immunology)
Examining committee member and department
Baksh, Shairaz (Pediatrics)
Foley, Edan (Medical Microbiology and Immunology)
Smiley, James (Medical Microbiology and Immunology)
Department
Department of Medical Microbiology and Immunology
Specialization

Date accepted
2010-08-03T17:17:35Z
Graduation date
2010-11
Degree
Master of Science
Degree level
Master's
Abstract
The classical Nuclear Factor kappa B (NF-κB) signaling pathway is an important regulator of inflammation and innate immune responses. Poxviruses, including vaccinia virus, encode multiple immune evasion proteins, including a growing number of NF-κB inhibitors. To determine if additional vaccinia virus gene products disrupted NF-κB signaling, we utilized VV811, a mutant virus missing 55 open reading frames and devoid of the known inhibitors of TNFα-induced NF-κB activation. NF-κB nuclear translocation was inhibited in VV811 infected cells stimulated with TNFα. Furthermore, VV811 infection suppressed IκBα degradation and resulted in accumulation of phosphorylated IκBα in cells stimulated with TNFα. Coimmunoprecipitation assays demonstrated that the inhibitory IκBα-p65-p50 complex was intact in VV811 infected cells, and, significantly, treatment with AraC revealed the involvement of late protein synthesis in stabilization of IκBα. This work indicates that unidentified inhibitors of NF-κB exist in vaccinia virus and illustrates the importance of NF-κB activation in the antiviral response.
Language
English
Rights
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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File title: University of Alberta
File author: Faculty of Graduate Studies and Research
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