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Open Access Research article

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

Laxmi Iyer Ravi1, Liang Li12, Richard Sutejo1, Hui Chen1, Pui San Wong3, Boon Huan Tan3 and Richard J Sugrue12*

Author affiliations

1 Division of Molecular Genetics and Cell Biology, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore

2 Singapore-MIT Alliance for Research & Technology (SMART), Centre for Life Sciences, 28 Medical Drive, Singapore 117456, Singapore

3 Detection and Diagnostics Laboratory, DSO National Laboratories, 27 Medical Drive, Singapore, 117510, Singapore

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Citation and License

BMC Genomics 2013, 14:190  doi:10.1186/1471-2164-14-190

Published: 18 March 2013

Abstract

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.

Keywords:
Respiratory syncytial virus; Macrophage transcriptome; Host response; Interferon; Cytokine induction