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Journal of Virology, June 2007, p. 5958-5967, Vol. 81, No. 11
0022-538X/07/$08.00+0     doi:10.1128/JVI.02220-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Host Transcription Profiles upon Primary Respiratory Syncytial Virus Infection ^,

Laboratory for Toxicology, Pathology and Genetics,¹ Laboratory for Vaccine-Preventable Diseases, National Institute for Public Health and the Environment, P.O. Box 1, 3720 BA Bilthoven, The Netherlands²

Received 10 October 2006/ Accepted 16 March 2007

Respiratory syncytial virus (RSV) is a common cause of severe lower respiratory tract infection in children. Severe RSV disease is related to an inappropriate immune response to RSV resulting in enhanced lung pathology which is influenced by host genetic factors. To gain insight into the early pathways of the pathogenesis of and immune response to RSV infection, we determined the transcription profiles of lungs and lymph nodes on days 1 and 3 after infection of mice. Primary RSV infection resulted in a rapid but transient innate, proinflammatory response, as exemplified by the induction of a large number of type I interferon-regulated genes and chemokine genes, genes involved in inflammation, and genes involved in antigen processing. Interestingly, this response is much stronger on day 1 than on day 3 after infection, indicating that the strong transcriptional response in the lung precedes the peak of viral replication. Surprisingly, the set of down-regulated genes was small and none of these genes displayed strong down-regulation. Responses in the lung-draining lymph nodes were much less prominent than lung responses and are suggestive of NK cell activation. Our data indicate that at time points prior to the peak of viral replication and influx of inflammatory cells, the local lung response, measured at the transcriptional level, has already dampened down. The processes and pathways induced shortly after RSV infection can now be used for the selection of candidate genes for human genetic studies of children with severe RSV infection.

Published ahead of print on 21 March 2007.

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