title: Formyl Peptide Receptor 2 Plays a Deleterious Role During Influenza A Virus Infections.
abstract: The pathogenesis of influenza A virus (IAV) infections is a multifactorial process that includes the replication capacity of the virus and a harmful inflammatory response to infection. Formyl peptide receptor 2 (FPR2) emerges as a central receptor in inflammatory processes controlling resolution of acute inflammation. Its role in virus pathogenesis has not been investigated yet.
  
  
  
  We used pharmacologic approaches to investigate the role of FPR2 during IAV infection in vitro and in vivo.
  
  
  
  In vitro, FPR2 expressed on A549 cells was activated by IAV, which harbors its ligand, annexin A1, in its envelope. FPR2 activation by IAV promoted viral replication through an extracellular-regulated kinase (ERK)-dependent pathway. In vivo, activating FPR2 by administering the agonist WKYMVm-NH2 decreased survival and increased viral replication and inflammation after IAV infection. This effect was abolished by treating the mice with U0126, a specific ERK pathway inhibitor, showing that, in vivo, the deleterious role of FPR2 also occurs through an ERK-dependent pathway. In contrast, administration of the FPR2 antagonist WRW4 protected mice from lethal IAV infections.
  
  
  
  These data show that viral replication and IAV pathogenesis depend on FPR2 signaling and suggest that FPR2 may be a promising novel strategy to treat influenza.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR_S 1062 INRA, UMR_INRA 1260, France Aix Marseille Université
authors.forename: Sergey
authors.initials: S
authors.lastname: Tcherniuk
authors.affiliation: IRSD, Université de Toulouse, INSERM, INRA, INP-ENVT, Université de Toulouse 3 Paul Sabatier.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Cenac
authors.affiliation: EA4610.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Comte
authors.affiliation: EA4610.
authors.forename: Julie
authors.initials: J
authors.lastname: Frouard
authors.affiliation: Centre Commun d'Imagerie Quantitative Lyon Est, SFR Santé Lyon-Est, University of Lyon, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Errazuriz-Cerda
authors.affiliation: Bulgarian Academy of Sciences, Stephan Angeloff Institute of Microbiology, Sofia.
authors.forename: Angel
authors.initials: A
authors.lastname: Galabov
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR_S 1062 INRA, UMR_INRA 1260, France Aix Marseille Université
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Morange
authors.affiliation: IRSD, Université de Toulouse, INSERM, INRA, INP-ENVT, Université de Toulouse 3 Paul Sabatier.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vergnolle
authors.affiliation: Inserm U1100 - Centre d'études des pathologies respiratoires Université F. Rabelais, Tours, France.
authors.forename: Mustapha
authors.initials: M
authors.lastname: Si-Tahar
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR_S 1062 INRA, UMR_INRA 1260, France Aix Marseille Université
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Alessi
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR_S 1062 INRA, UMR_INRA 1260, France Aix Marseille Université
authors.forename: Béatrice
authors.initials: B
authors.lastname: Riteau
mesh_terms: D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000502:physiology / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D009980:Influenza A virus / Q000472:pathogenicity* / Q000502:physiology; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000473:pathology* / Q000821:virology*; D044042:Receptors, Formyl Peptide / Q000378:metabolism*; D044067:Receptors, Lipoxin / Q000378:metabolism*; D014774:Virulence; D014779:Virus Replication
chemical_list: C105101:FPR2 protein, human; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; C481578:formyl peptide receptor 2, mouse
keywords: formyl peptide receptor 2; host immune response; influenza; influenza virus