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Transcriptomic and proteomic analyses reveal new insights into the regulation of immune pathways during adenovirus type 2 infection
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
Monash Univ, Cent Clin Sch, Australian Ctr Blood Dis, Clayton, Vic, Australia.
Univ Alcala De Henares, Dept Analyt Chem Phys Chem & Chem Engn, Madrid, Spain.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.ORCID iD: 0000-0002-9510-3816
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2019 (English)In: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 19, article id 15Article in journal (Refereed) Published
Abstract [en]

Background: Human adenovirus (Ad) infection leads to the changes of host cell gene expression and biosynthetic processes. Transcriptomics in adenovirus type 2 (Ad2)-infected lung fibroblasts (IMR-90) cells has previously been studied using RNA sequencing. However, this study included only two time points (12 and 24 hpi) using constrained 76bp long sequencing reads. Therefore, a more detailed study of transcription at different phases of infection using an up-graded sequencing technique is recalled. Furthermore, the correlation between transcription and protein expression needs to be addressed.

Results: In total, 3556 unique cellular genes were identified as differentially expressed at the transcriptional level with more than 2-fold changes in Ad2-infected cells as compared to non-infected cells by using paired-end sequencing. Based on the kinetics of the gene expression changes at different times after infection, these RNAs fell into 20 clusters. Among them, cellular genes involved in immune response were highly up-regulated in the early phase before becoming down-regulated in the late phase. Comparison of differentially expressed genes at transcriptional and posttranscriptional levels revealed low correlation. Particularly genes involved in cellular immune pathways showed a negative correlation. Here, we highlight the genes which expose inconsistent expression profiles with an emphasis on key factors in cellular immune pathways including NFB, JAK/STAT, caspases and MAVS. Different from their transcriptional profiles with up- and down-regulation in the early and late phase, respectively, these proteins were up-regulated in the early phase and were sustained in the late phase. A surprising finding was that the target genes of the sustained activators failed to show response.

Conclusion: There were features common to genes which play important roles in cellular immune pathways. Their expression was stimulated at both RNA and protein levels during the early phase. In the late phase however, their transcription was suppressed while protein levels remained stable. These results indicate that Ad2 and the host cell use different strategies to regulate cellular immune pathways. A control mechanism at the post-translational level must thus exist which is under the control of Ad2.

Place, publisher, year, edition, pages
BMC , 2019. Vol. 19, article id 15
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Microbiology
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URN: urn:nbn:se:uu:diva-375871DOI: 10.1186/s12866-018-1375-5ISI: 000455585900003PubMedID: 30642258OAI: oai:DiVA.org:uu-375871DiVA, id: diva2:1285249
Funder
Swedish Foundation for Strategic Research Available from: 2019-02-04 Created: 2019-02-04 Last updated: 2019-02-04Bibliographically approved

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