Identification of common biological pathways and drug targets across multiple respiratory viruses based on human host gene expression analysis.

Pandemic and seasonal respiratory viruses are a major global health
concern. Given the genetic diversity of respiratory viruses and the emergence of 
drug resistant strains, the targeted disruption of human host-virus interactions 
is a potential therapeutic strategy for treating multi-viral infections. The
availability of large-scale genomic datasets focused on host-pathogen
interactions can be used to discover novel drug targets as well as potential
opportunities for drug repositioning.
METHODS/RESULTS: In this study, we performed a large-scale analysis of microarray
datasets involving host response to infections by influenza A virus, respiratory 
syncytial virus, rhinovirus, SARS-coronavirus, metapneumonia virus,
coxsackievirus and cytomegalovirus. Common genes and pathways were found through 
a rigorous, iterative analysis pipeline where relevant host mRNA expression
datasets were identified, analyzed for quality and gene differential expression, 
then mapped to pathways for enrichment analysis. Possible repurposed drugs
targets were found through database and literature searches. A total of 67 common
biological pathways were identified among the seven different respiratory viruses
analyzed, representing fifteen laboratories, nine different cell types, and seven
different array platforms. A large overlap in the general immune response was
observed among the top twenty of these 67 pathways, adding validation to our
analysis strategy. Of the top five pathways, we found 53 differentially expressed
genes affected by at least five of the seven viruses. We suggest five new
therapeutic indications for existing small molecules or biological agents
targeting proteins encoded by the genes F3, IL1B, TNF, CASP1 and MMP9. Pathway
enrichment analysis also identified a potential novel host response, the
Parkin-Ubiquitin Proteasomal System (Parkin-UPS) pathway, which is known to be
involved in the progression of neurodegenerative Parkinson's disease.
CONCLUSIONS: Our study suggests that multiple and diverse respiratory viruses
invoke several common host response pathways. Further analysis of these pathways 
suggests potential opportunities for therapeutic intervention.
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