Cargando…

Transcriptomic and proteomic analyses reveal new insights into the regulation of immune pathways during adenovirus type 2 infection

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 p...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhao, Hongxing, Chen, Maoshan, Valdés, Alberto, Lind, Sara Bergström, Pettersson, Ulf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332865/
https://www.ncbi.nlm.nih.gov/pubmed/30642258
http://dx.doi.org/10.1186/s12866-018-1375-5
_version_ 1783387446576152576
author Zhao, Hongxing
Chen, Maoshan
Valdés, Alberto
Lind, Sara Bergström
Pettersson, Ulf
author_facet Zhao, Hongxing
Chen, Maoshan
Valdés, Alberto
Lind, Sara Bergström
Pettersson, Ulf
author_sort Zhao, Hongxing
collection PubMed
description 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 76 bp 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 NFκB, 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12866-018-1375-5) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-6332865
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-63328652019-01-23 Transcriptomic and proteomic analyses reveal new insights into the regulation of immune pathways during adenovirus type 2 infection Zhao, Hongxing Chen, Maoshan Valdés, Alberto Lind, Sara Bergström Pettersson, Ulf BMC Microbiol Research Article 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 76 bp 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 NFκB, 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12866-018-1375-5) contains supplementary material, which is available to authorized users. BioMed Central 2019-01-14 /pmc/articles/PMC6332865/ /pubmed/30642258 http://dx.doi.org/10.1186/s12866-018-1375-5 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Zhao, Hongxing
Chen, Maoshan
Valdés, Alberto
Lind, Sara Bergström
Pettersson, Ulf
Transcriptomic and proteomic analyses reveal new insights into the regulation of immune pathways during adenovirus type 2 infection
title Transcriptomic and proteomic analyses reveal new insights into the regulation of immune pathways during adenovirus type 2 infection
title_full Transcriptomic and proteomic analyses reveal new insights into the regulation of immune pathways during adenovirus type 2 infection
title_fullStr Transcriptomic and proteomic analyses reveal new insights into the regulation of immune pathways during adenovirus type 2 infection
title_full_unstemmed Transcriptomic and proteomic analyses reveal new insights into the regulation of immune pathways during adenovirus type 2 infection
title_short Transcriptomic and proteomic analyses reveal new insights into the regulation of immune pathways during adenovirus type 2 infection
title_sort transcriptomic and proteomic analyses reveal new insights into the regulation of immune pathways during adenovirus type 2 infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332865/
https://www.ncbi.nlm.nih.gov/pubmed/30642258
http://dx.doi.org/10.1186/s12866-018-1375-5
work_keys_str_mv AT zhaohongxing transcriptomicandproteomicanalysesrevealnewinsightsintotheregulationofimmunepathwaysduringadenovirustype2infection
AT chenmaoshan transcriptomicandproteomicanalysesrevealnewinsightsintotheregulationofimmunepathwaysduringadenovirustype2infection
AT valdesalberto transcriptomicandproteomicanalysesrevealnewinsightsintotheregulationofimmunepathwaysduringadenovirustype2infection
AT lindsarabergstrom transcriptomicandproteomicanalysesrevealnewinsightsintotheregulationofimmunepathwaysduringadenovirustype2infection
AT petterssonulf transcriptomicandproteomicanalysesrevealnewinsightsintotheregulationofimmunepathwaysduringadenovirustype2infection