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How adenovirus perturb cellular gene regulation when propagated in primary cells
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
Manuscript (Other academic)
URN: urn:nbn:se:uu:diva-95073OAI: oai:DiVA.org:uu-95073DiVA: diva2:169143
Available from: 2006-10-27 Created: 2006-10-27 Last updated: 2010-01-13Bibliographically approved
In thesis
1. Global Profiling of Host Cell Gene Expression During Adenovirus Infection
Open this publication in new window or tab >>Global Profiling of Host Cell Gene Expression During Adenovirus Infection
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

To investigate mechanisms involved in virus-host interactions, global changes in host gene expression were examined during infection with adenovirus type 2 (Ad2) using cDNA microarray technology.

In paper I and II, transcriptional changes in HeLa cells were investigated during the early and late phase of infection, respectively. A limited number of genes, mainly implicated in cell growth and antiviral defence, were found to be differentially expressed in the early phase, whereas modulation of host cell gene expression during the late phase was augmented and mainly focused on growth inhibition and cell architecture.

The experimental set-up was then redesigned to follow transcriptional regulatory events in growth synchronised, human primary lung fibroblasts. The immediate response of the host cell within two hours of infection was investigated in paper III, revealing a transient induction of a small number of cellular alert genes. This was followed by an expanded time course presented in paper IV, which included gene expression profiling at eight consecutive time points throughout the infectious cycle. The results indicated that specific sets of cellular genes were targeted at different stages of the infection, and four distinct periods were identified.

In summary, the studies presented in this thesis demonstrate that adenovirus interferes with many cellular processes during the progression of infection to optimize the cellular environment for viral replication. These include cell cycle control, cell growth and growth inhibition, as well as DNA, RNA and protein metabolism. However, a transient induction of cellular genes involved in immune response and growth inhibition was observed before the onset of viral gene expression. During the very late stages of infection, the expression of a large number of genes involved in maintaining the cell structure was down-regulated, presumably to facilitate the spread of progeny virus.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 57 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 195
Genetic engineering, Adenovirus, Microarray, Gene expression, Host-virus interaction, Genteknik
urn:nbn:se:uu:diva-7221 (URN)91-554-6704-0 (ISBN)
Public defence
2006-11-17, Rudbecksalen, Rudbecklaboratoriet, Dag Hammarskjölds väg 20, Uppsala, 09:15
Available from: 2006-10-27 Created: 2006-10-27Bibliographically approved

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