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Combined Genetic and Chemical Capsid Modifications of Adenovirus-Based Gene Transfer Vectors for Shielding and Targeting
Published on: October 26, 2018
How adenovirus strives to control cellular gene expression
Hongxing Zhao1, Fredrik Granberg, Ulf Pettersson
1Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, S-751 85 Uppsala, Sweden. Hongxing.Zhao@genpat.uu.se <Hongxing.Zhao@genpat.uu.se>
Human adenovirus infection alters host cell gene expression, impacting cell cycle, growth, and structure. This study details the dynamic changes in gene regulation throughout the viral infection process.
Area of Science:
- Virology
- Molecular Biology
- Genomics
Background:
- Human adenoviruses are significant human pathogens.
- Understanding host-pathogen interactions at the gene expression level is crucial for developing antiviral strategies.
Purpose of the Study:
- To comprehensively analyze host cell gene expression changes during human adenovirus infection in primary human lung fibroblasts.
- To delineate the temporal patterns of cellular gene deregulation throughout the viral life cycle.
Main Methods:
- Utilized cDNA microarrays for high-throughput analysis of host cell gene expression.
- Employed synchronized primary human lung fibroblasts to ensure a controlled experimental system.
- Analyzed differential gene expression ( > 2-fold change) for 988 unique genes.
Main Results:
- Identified 988 differentially expressed genes, with expression profiles correlating to infection progression.
- Characterized four distinct periods of cellular gene deregulation: immediate response, cell cycle/antiviral response, viral DNA replication, and late-phase structural targeting.
- Observed viral manipulation of host TGF-beta, Wnt signaling, and apoptotic pathways.
Conclusions:
- Human adenovirus infection induces complex and dynamic alterations in host cell gene expression.
- The virus actively modulates host pathways to facilitate its replication and propagation.
- These findings provide insights into adenovirus pathogenesis and potential therapeutic targets.
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