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Gene profiling in enteroviral heart disease Yanagawa, Bobby
Abstract
The application of high-throughput genomical strategies and bioinformatical tools coupled with established molecular techniques allows researchers to gain new insights into the pathogenesis of infectious diseases. In humans, coxsackievirus B3 (CVB3) is the primary etiological agent of viral myocarditis, an inflammatory disease process involving the heart muscle. Specific therapy is currently unavailable. Viral myocarditis is a complex multiphasic infectious-inflammatory-reparative process. To address this temporal dimensionality, microarrays and non-array-based molecular techniques and histological and functional assays were used to further define enteroviral pathogenesis and its relation to heart failure. A re-analysed cDNA array-based dataset and an Affymetrix GeneChip®- based dataset from the murine heart during acute viremic, inflammatory and reparative stages were mined and compared. Global decreases in expression of metabolic and mitochondrial genes, increases in signalling, matrix and contractile protein genes, and distinctive patterns for genes in other functional groups are described. The transcript and protein profiles of heat shock protein 27, Muscle LIM protein and cathepsin L were confirmed using RT-PCR and immunohistochemistry, respectively. To focus on direct virus and host cell interactions, the transcriptional profile of CVB3-infected HeLa cells was investigated. Notably, increased expression of transcription factor c-fos downstream of extracellular signal-related kinase was found, a pathway our laboratory has previously shown to be important for virus replication and pathogenesis. The in vitro array experiment included a MEKl inhibitor treatment group. Commercial and in-house bioinformatical filtration, cluster analysis and visualization tools were used to determine potential gene targets downstream in the ERK pathway in the setting of CVB3 infection. Marked upregulation of oncogenes, serpins and matrix metalloproteinase genes, among others, were found in infected HeLa cells and in the heart. Together, our animal and cell culture array studies have contributed insight into host responses to enteroviral infections from which new testable hypotheses have been generated.
Item Metadata
Title |
Gene profiling in enteroviral heart disease
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
2004
|
Description |
The application of high-throughput genomical strategies and bioinformatical tools coupled
with established molecular techniques allows researchers to gain new insights into the
pathogenesis of infectious diseases. In humans, coxsackievirus B3 (CVB3) is the primary
etiological agent of viral myocarditis, an inflammatory disease process involving the heart
muscle. Specific therapy is currently unavailable. Viral myocarditis is a complex
multiphasic infectious-inflammatory-reparative process. To address this temporal
dimensionality, microarrays and non-array-based molecular techniques and histological and
functional assays were used to further define enteroviral pathogenesis and its relation to
heart failure. A re-analysed cDNA array-based dataset and an Affymetrix GeneChip®-
based dataset from the murine heart during acute viremic, inflammatory and reparative
stages were mined and compared. Global decreases in expression of metabolic and
mitochondrial genes, increases in signalling, matrix and contractile protein genes, and
distinctive patterns for genes in other functional groups are described. The transcript and
protein profiles of heat shock protein 27, Muscle LIM protein and cathepsin L were
confirmed using RT-PCR and immunohistochemistry, respectively. To focus on direct
virus and host cell interactions, the transcriptional profile of CVB3-infected HeLa cells was
investigated. Notably, increased expression of transcription factor c-fos downstream of
extracellular signal-related kinase was found, a pathway our laboratory has previously
shown to be important for virus replication and pathogenesis. The in vitro array
experiment included a MEKl inhibitor treatment group. Commercial and in-house
bioinformatical filtration, cluster analysis and visualization tools were used to determine
potential gene targets downstream in the ERK pathway in the setting of CVB3 infection.
Marked upregulation of oncogenes, serpins and matrix metalloproteinase genes, among
others, were found in infected HeLa cells and in the heart. Together, our animal and cell
culture array studies have contributed insight into host responses to enteroviral infections
from which new testable hypotheses have been generated.
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Extent |
33250111 bytes
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Genre | |
Type | |
File Format |
application/pdf
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Language |
eng
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Date Available |
2009-11-27
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Provider |
Vancouver : University of British Columbia Library
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Rights |
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
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DOI |
10.14288/1.0099788
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
2004-05
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Campus | |
Scholarly Level |
Graduate
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Aggregated Source Repository |
DSpace
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Item Citations and Data
Rights
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.