Protective Role of LGP2 in Influenza Virus Pathogenesis

• Published in: The Journal of infectious diseases 2014-07, Vol.210 (2), p.214-223
• Main Authors: Si-Tahar, Mustapha, Blanc, Fany, Furio, Laetitia, Chopy, Damien, Balloy, Viviane, Lafon, Monique, Chignard, Michel, Fiette, Laurence, Langa, Francina, Charneau, Pierre, Pothlichet, Julien
• Format: Article
• Language: English
• Subjects: Animals; Antivirals; Biological and medical sciences; DEAD Box Protein 58; DEAD-box RNA Helicases; DEAD-box RNA Helicases - metabolism; Disease Models, Animal; Epithelial cells; Fundamental and applied biological sciences. Psychology; Gene Expression; Host-Pathogen Interactions; Human health and pathology; Immunology; Infections; Infectious diseases; Inflammation Mediators; Inflammation Mediators - analysis; Influenza A virus; Influenza A virus - physiology; Leukocytes; Leukocytes - immunology; Life Sciences; Lungs; Medical sciences; Messenger RNA; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microbiology; Miscellaneous; Orthomyxoviridae Infections; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - pathology; Pulmonology and respiratory tract; RNA Helicases; RNA Helicases - metabolism; Signal Transduction; Survival Analysis; T lymphocytes; Virology; Viruses
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiu076

Influenza A virus triggers a contagious respiratory disease that can cause considerable morbidity and mortality. Using an in vitro approach, we previously demonstrated that the pattern recognition receptor retinoic acidinducible gene I (RIG-I) plays a key role in influenza A virus-mediated immune response. However, the importance of RIG-I signaling in vivo has not been thoroughly examined, because of the lack of an appropriate mouse models. To circumvent this issue, we generated a new transgenic mouse overexpressing LGP2 (hereafter, "LGP2 TG mice"), a major regulator of the RIG-I signaling pathway. The time course of several parameters was compared in infected wild-type and LGP2 TG mice. We found that LGP2 TG mice displayed significantly reduced inflammatory mediators and a lower leukocyte infiltration into the bronchoalveolar airspace. More importantly, LGP2 TG mice had a significant survival advantage. Hence, our in vivo study reveals that LGP2 is a major downregulator of the influenza A virus-triggered detrimental inflammatory response.