Systems-level comparison of host-responses elicited by avian H5N1 and seasonal H1N1 influenza viruses in primary human macrophages.

Abstract : Human disease caused by highly pathogenic avian influenza (HPAI) H5N1 can lead to a rapidly progressive viral pneumonia leading to acute respiratory distress syndrome. There is increasing evidence from clinical, animal models and in vitro data, which suggests a role for virus-induced cytokine dysregulation in contributing to the pathogenesis of human H5N1 disease. The key target cells for the virus in the lung are the alveolar epithelium and alveolar macrophages, and we have shown that, compared to seasonal human influenza viruses, equivalent infecting doses of H5N1 viruses markedly up-regulate pro-inflammatory cytokines in both primary cell types in vitro. Whether this H5N1-induced dysregulation of host responses is driven by qualitative (i.e activation of unique host pathways in response to H5N1) or quantitative differences between seasonal influenza viruses is unclear. Here we used microarrays to analyze and compare the gene expression profiles in primary human macrophages at 1, 3, and 6 h after infection with H5N1 virus or low-pathogenic seasonal influenza A (H1N1) virus. We found that host responses to both viruses are qualitatively similar with the activation of nearly identical biological processes and pathways. However, in comparison to seasonal H1N1 virus, H5N1 infection elicits a quantitatively stronger host inflammatory response including type I interferon (IFN) and tumor necrosis factor (TNF)-alpha genes. A network-based analysis suggests that the synergy between IFN-beta and TNF-alpha results in an enhanced and sustained IFN and pro-inflammatory cytokine response at the early stage of viral infection that may contribute to the viral pathogenesis and this is of relevance to the design of novel therapeutic strategies for H5N1 induced respiratory disease.
Document type :
Journal articles
Complete list of metadatas

Cited literature [44 references]  Display  Hide  Download

https://hal-riip.archives-ouvertes.fr/pasteur-00588914
Contributor : Francois Kien <>
Submitted on : Wednesday, April 27, 2011 - 7:01:02 AM
Last modification on : Tuesday, August 27, 2019 - 3:08:01 PM
Long-term archiving on : Thursday, July 28, 2011 - 2:34:39 AM

File

Lee_et_al_PLoS_One_2009.pdf
Publisher files allowed on an open archive

Identifiers

Collections

Citation

Suki M Y Lee, Jennifer L Gardy, C. Y. Cheung, Timothy K W Cheung, Kenrie P Y Hui, et al.. Systems-level comparison of host-responses elicited by avian H5N1 and seasonal H1N1 influenza viruses in primary human macrophages.. PLoS ONE, Public Library of Science, 2009, 4 (12), pp.e8072. ⟨10.1371/journal.pone.0008072⟩. ⟨pasteur-00588914⟩

Share

Metrics

Record views

197

Files downloads

169