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J Infect Dis. 2016 Jul 15;214(2):237-47. doi: 10.1093/infdis/jiw127. Epub 2016 Mar 30.

Formyl Peptide Receptor 2 Plays a Deleterious Role During Influenza A Virus Infections.

Author information

1
Institut National de la Santé et de la Recherche Médicale (INSERM), UMR_S 1062 INRA, UMR_INRA 1260, France Aix Marseille Université
2
IRSD, Université de Toulouse, INSERM, INRA, INP-ENVT, Université de Toulouse 3 Paul Sabatier.
3
EA4610.
4
Centre Commun d'Imagerie Quantitative Lyon Est, SFR Santé Lyon-Est, University of Lyon, France.
5
Bulgarian Academy of Sciences, Stephan Angeloff Institute of Microbiology, Sofia.
6
Inserm U1100 - Centre d'études des pathologies respiratoires Université F. Rabelais, Tours, France.

Abstract

BACKGROUND:

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.

METHODS:

We used pharmacologic approaches to investigate the role of FPR2 during IAV infection in vitro and in vivo.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

formyl peptide receptor 2; host immune response; influenza; influenza virus

PMID:
27034344
DOI:
10.1093/infdis/jiw127
[Indexed for MEDLINE]

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