Host Response Comparison of H1N1- and H5N1-Infected Mice Identifies Two Potential Death Mechanisms

• Published in: International journal of molecular sciences Vol. 18; no. 8; p. 1631
• Main Authors: Leymarie, Olivier, Meyer, Léa, Hervé, Pierre-Louis, Da Costa, Bruno, Delmas, Bernard, Chevalier, Christophe, Le Goffic, Ronan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27-07-2017; MDPI
• Subjects: Animals; Avian flu; Bioinformatics; Cluster Analysis; Edema; Epistasis, Genetic; Female; Gene Expression Profiling; Gene Ontology; H1N1; H5N1; host response; Host-Pathogen Interactions; Influenza A; Influenza A Virus, H1N1 Subtype - physiology; Influenza A Virus, H5N1 Subtype - physiology; influenza virus; Interleukin-6 - genetics; Interleukin-6 - metabolism; Life Sciences; Lung - metabolism; Lung - pathology; Lungs; Mice, Inbred C57BL; Models, Biological; Molecular modelling; Morbidity; mouse model; Orthomyxoviridae Infections - genetics; Orthomyxoviridae Infections - pathology; Orthomyxoviridae Infections - virology; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Survival Analysis; transcriptome; Viral Load; host response; influenza virus; H5N1; mouse model; H1N1; transcriptome
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms18081631

Highly pathogenic influenza A viruses (IAV) infections represent a serious threat to humans due to their considerable morbidity and mortality capacities. A good understanding of the molecular mechanisms responsible for the acute lung injury observed during this kind of infection is essential to design adapted therapies. In the current study, using an unbiased transcriptomic approach, we compared the host-responses of mice infected with two different subtypes of IAV: H1N1 vs. H5N1. The host-response comparison demonstrated a clear difference between the transcriptomic profiles of H1N1- and H5N1-infected mice despite identical survival kinetics and similar viral replications. The ontological analysis of the two transcriptomes showed two probable causes of death: induction of an immunopathological state of the lung for the H1N1 strain vs. development of respiratory dysfunction in the case of the H5N1 IAV. Finally, a clear signature responsible for lung edema was specifically associated with the H5N1 infection. We propose a potential mechanism of edema development based on predictive bioinformatics tools.