A systems-based approach to analyse the host response in murine lung macrophages challenged with respiratory syncytial virus

Background: Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract infection in young children. The degree of disease severity is determined by the host response to infection. Lung macrophages play an important early role in the host response to infection and we have used...

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Main Authors: Sutejo, Richard, Chen, Hui, Wong, Pui San, Tan, Boon Huan, Sugrue, Richard J., Ravi, Laxmi Iyer, Li, Liang
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2013
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Online Access:https://hdl.handle.net/10356/96326
http://hdl.handle.net/10220/10176
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spelling sg-ntu-dr.10356-963262023-02-28T17:04:16Z A systems-based approach to analyse the host response in murine lung macrophages challenged with respiratory syncytial virus Sutejo, Richard Chen, Hui Wong, Pui San Tan, Boon Huan Sugrue, Richard J. Ravi, Laxmi Iyer Li, Liang School of Biological Sciences DRNTU::Science::Biological sciences Background: Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract infection in young children. The degree of disease severity is determined by the host response to infection. Lung macrophages play an important early role in the host response to infection and we have used a systems-based approach to examine the host response in RSV-infected lung-derived macrophage cells. Results: Lung macrophage cells could be efficiently infected (>95%) with RSV in vitro, and the expression of several virus structural proteins could be detected. Although we failed to detect significant levels of virus particle production, virus antigen could be detected up until 96 hours post-infection (hpi). Microarray analysis indicated that 20,086 annotated genes were expressed in the macrophage cells, and RSV infection induced an 8.9% and 11.3% change in the global gene transcriptome at 4 hpi and 24 hpi respectively. Genes showing up-regulated expression were more numerous and exhibited higher changes in expression compared to genes showing down-regulated expression. Based on gene ontology, genes with cytokine, antiviral, cell death, and signal transduction functions showed the highest increases in expression, while signalling transduction, RNA binding and protein kinase genes showed the greatest reduction in expression levels. Analysis of the global gene expression profile using pathway enrichment analysis confirmed that up-regulated expression of pathways related to pathogen recognition, interferon signalling and antigen presentation occurred in the lung macrophage cells challenged with RSV. Conclusion: Our data provided a comprehensive analysis of RSV-induced gene expression changes in lung macrophages. Although virus gene expression was detected, our data was consistent with an abortive infection and this correlated with the activation of several antivirus signalling pathways such as interferon type I signalling and cell death signalling. RSV infection induced a relatively large increase in pro-inflammatory cytokine expression, however the maintenance of this pro-inflammatory response was not dependent on the production of infectious virus particles. The sustained pro-inflammatory response even in the absence of a productive infection suggests that drugs that control the pro-inflammatory response may be useful in the treatment of patients with severe RSV infection. Published version 2013-06-11T04:39:59Z 2019-12-06T19:29:01Z 2013-06-11T04:39:59Z 2019-12-06T19:29:01Z 2013 2013 Journal Article Ravi, L. I., Li, L., Sutejo, R., Chen, H., Wong, P. S., Tan, B. H., & Sugrue, R. J. (2013). A systems-based approach to analyse the host response in murine lung macrophages challenged with respiratory syncytial virus. BMC Genomics, 14(1), 190-. https://hdl.handle.net/10356/96326 http://hdl.handle.net/10220/10176 10.1186/1471-2164-14-190 23506210 en BMC genomics © 2013 Ravi et al. This paper was published in BMC Genomics and is made available as an electronic reprint (preprint) with permission of Ravi et al. The paper can be found at the following official DOI: [http://dx.doi.org/10.1186/1471-2164-14-190].  One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences
spellingShingle DRNTU::Science::Biological sciences
Sutejo, Richard
Chen, Hui
Wong, Pui San
Tan, Boon Huan
Sugrue, Richard J.
Ravi, Laxmi Iyer
Li, Liang
A systems-based approach to analyse the host response in murine lung macrophages challenged with respiratory syncytial virus
description Background: Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract infection in young children. The degree of disease severity is determined by the host response to infection. Lung macrophages play an important early role in the host response to infection and we have used a systems-based approach to examine the host response in RSV-infected lung-derived macrophage cells. Results: Lung macrophage cells could be efficiently infected (>95%) with RSV in vitro, and the expression of several virus structural proteins could be detected. Although we failed to detect significant levels of virus particle production, virus antigen could be detected up until 96 hours post-infection (hpi). Microarray analysis indicated that 20,086 annotated genes were expressed in the macrophage cells, and RSV infection induced an 8.9% and 11.3% change in the global gene transcriptome at 4 hpi and 24 hpi respectively. Genes showing up-regulated expression were more numerous and exhibited higher changes in expression compared to genes showing down-regulated expression. Based on gene ontology, genes with cytokine, antiviral, cell death, and signal transduction functions showed the highest increases in expression, while signalling transduction, RNA binding and protein kinase genes showed the greatest reduction in expression levels. Analysis of the global gene expression profile using pathway enrichment analysis confirmed that up-regulated expression of pathways related to pathogen recognition, interferon signalling and antigen presentation occurred in the lung macrophage cells challenged with RSV. Conclusion: Our data provided a comprehensive analysis of RSV-induced gene expression changes in lung macrophages. Although virus gene expression was detected, our data was consistent with an abortive infection and this correlated with the activation of several antivirus signalling pathways such as interferon type I signalling and cell death signalling. RSV infection induced a relatively large increase in pro-inflammatory cytokine expression, however the maintenance of this pro-inflammatory response was not dependent on the production of infectious virus particles. The sustained pro-inflammatory response even in the absence of a productive infection suggests that drugs that control the pro-inflammatory response may be useful in the treatment of patients with severe RSV infection.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Sutejo, Richard
Chen, Hui
Wong, Pui San
Tan, Boon Huan
Sugrue, Richard J.
Ravi, Laxmi Iyer
Li, Liang
format Article
author Sutejo, Richard
Chen, Hui
Wong, Pui San
Tan, Boon Huan
Sugrue, Richard J.
Ravi, Laxmi Iyer
Li, Liang
author_sort Sutejo, Richard
title A systems-based approach to analyse the host response in murine lung macrophages challenged with respiratory syncytial virus
title_short A systems-based approach to analyse the host response in murine lung macrophages challenged with respiratory syncytial virus
title_full A systems-based approach to analyse the host response in murine lung macrophages challenged with respiratory syncytial virus
title_fullStr A systems-based approach to analyse the host response in murine lung macrophages challenged with respiratory syncytial virus
title_full_unstemmed A systems-based approach to analyse the host response in murine lung macrophages challenged with respiratory syncytial virus
title_sort systems-based approach to analyse the host response in murine lung macrophages challenged with respiratory syncytial virus
publishDate 2013
url https://hdl.handle.net/10356/96326
http://hdl.handle.net/10220/10176
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