COVID-19 researchGene: FPR2
There is evidence that FPR2 is involved in viral replication and inflammatory response to the Influenza virus.
Those papers (28928730, 27034344,29738458,29127186) say that FPR2 promotes viral replication and antagonists provide hope for selective treatment. However, it should be noted that the authors of the first 3 papers are from the same institutions in France(Marie-Christine Alessi). In contrast, this paper (31398292) says that it has protective effect against viral infection. I would recommend that it should be involved in our panel, in either case, to further investigate and validate the existing evidence.
The Annexin A1 Receptor FPR2 Regulates the Endosomal Export of Influenza Virus(29738458)
The Formyl Peptide Receptor 2 (FPR2) is a novel promising target for the treatment of influenza. During viral infection, FPR2 is activated by annexinA1, which is present in the envelope of influenza viruses; this activation promotes virus replication. Here, we investigated whether blockage of FPR2 would affect the genome trafficking of influenza virus. We found that, upon infection and cell treatment with the specific FPR2 antagonist WRW4 or the anti-FPR2 monoclonal antibody, FN-1D6-AI, influenza viruses were blocked into endosomes. This effect was independent on the strain and was observed for H1N1 and H3N2 viruses. In addition, blocking FPR2signaling in alveolar lung A549 epithelial cells with the monoclonal anti-FPR2 antibody significantly inhibited virus replication. Altogether, these results show that FPR2signaling interferes with the endosomal trafficking of influenza viruses and provides, for the first time, the proof of concept that monoclonal antibodies directed against FPR2 inhibit virus replication. Antibodies-based therapeutics have emerged as attractive reagents in infectious diseases. Thus, this study suggests that the use of anti-FPR2 antibodies against influenza hold great promise for the future.
The Annexin A1/FPR2 Signaling Axis Expands Alveolar Macrophages, Limits Viral Replication, and Attenuates Pathogenesis in the Murine Influenza A Virus Infection Model(PMID: 31398292)
we investigated AnxA1-mediated FPR2 activation on influenza A virus (IAV) infection in the murine model. AnxA1-treated mice displayed significantly attenuated pathology upon a subsequent IAV infection with significantly improved survival, impaired viral replication in the respiratory tract, and less severe lung damage. The AnxA1-mediated protection against IAV infection was not caused by priming of the type I IFN response but was associated with an increase in the number of alveolar macrophages (AMs) and enhanced pulmonary expression of the AM-regulating cytokine granulocyte-M-CSF (GM-CSF). Both AnxA1-mediated increase in AM levels and GM-CSF production were abrogated when mouse (m)FPR2 signaling was antagonized but remained up-regulated in mice genetically deleted for mFPR1, an mFPR2 isoform also serving as AnxA1 receptor. Our results indicate a novel protective function of the AnxA1-FPR2 signaling axis in IAV pathology via GM-CSF-associated maintenance of AMs, expanding knowledge on the potential use of proresolving mediators in host defense against pathogens.
Formyl Peptide Receptor 2 Is Regulated by RNA Mimics and Viruses Through an IFN-β-STAT3-dependent Pathway
In this study, we show that the activation of TLR3 and TLR7 induces the up-regulation of FPR2. We provide evidence that signal transducer and activator of transcription 3 (STAT3) phosphorylation is critical for the induction of FPR2 by double-stranded RNA, but not single-stranded RNA viral mimetics. The use of bone marrow-derived macrophages (BMDMs) from IFN-αβ receptor-deficient mice revealed that signaling via the type I IFN-STAT3 pathway is essential for FPR2 induction. We demonstrate that virus infection with enterovirus 71 and H1N1 PR8 influenza virus results in increased FPR2 expression. Inhibition of STAT3 phosphorylation in virus-infected cells repressed the induction of FPR2, which led to a reduction in viral loads. Finally, the absence of FPR2 in murine BMDMs resulted in lower viral loads, which suggests that FPR2 may be important for virus replication
Formyl Peptide Receptor 2 Plays a Deleterious Role During Influenza A Virus Infections(PMID: 27034344)
The pathogenesis of influenza A virus (IAV) infections is a multifactorial process that includes the replication capacity of the virus and 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.
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.
FPR2: A Novel Promising Target for the Treatment of Influenza
FPR2 is also used by viruses for their own profit. Annexin A1, one of the multiple ligands of FPR2, is incorporated in the budding virus membrane of influenza A viruses (IAV). Thereby, once IAV infects a host cell, FPR2 is activated. FPR2-signaling leads to an increase in viral replication, a dysregulation of the host immune response and severe disease. Conversely, experiments using FPR2 antagonists in a preclinical model of IAV infections in mice showed that blocking FPR2 protects animals from lethal infections. Thus, FPR2 represents a very attractive host target against influenza.
Created: 10 Apr 2020, 6:46 a.m. | Last Modified: 10 Apr 2020, 6:46 a.m.
Panel Version: 0.81
Comment on list classification: Upgrading to Green based on expert review
Created: 22 Apr 2020, 4:36 p.m. | Last Modified: 22 Apr 2020, 4:36 p.m.
Panel Version: 0.136
FPR2 is a seven transmembrane G protein-coupled receptor, which plays an important role in sensing of bacteria and modulation of immune responses
Mouse model PMID: 31908042 Fpr2/3 knockout (KO) mice and wild‐type (WT) controls were infected intranasally with S pneumoniae. AnxA1 and Fpr2/3 KO mice were highly susceptible to infection, displaying uncontrolled inflammation, increased bacterial dissemination, and pulmonary dysfunction compared to WT animals
PMID: 28928730 The review gives an overview on the pathogenesis of influenza with a focus on the role of FPR2 and discusses the advantages of using FPR2 antagonists to treat the flu. Preclinical studies have proven that FPR2 antagonists efficiently protect mice against IAV infections, by inhibiting viral replication and deleterious inflammation of the lungs
Created: 8 Apr 2020, 1:59 p.m. | Last Modified: 8 Apr 2020, 2:04 p.m.
Panel Version: 0.74
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
No evident link to immunodeficiency
Created: 11 Jun 2018, 2:24 p.m.
External expert review notes Red status due to no evident link to immunodeficiency, so I have kept this gene Red on this panel
Created: 12 Jun 2018, 3:03 p.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: Formyl peptide receptor, PanelApp HGNC gene symbol check: FPR2, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Phagocytic disorders / Localized juvenile peridontitis / Localized juvenile peridontitis
Created: 17 Apr 2018, 12:29 p.m.
Publications for gene: FPR2 were set to
Gene: fpr2 has been classified as Green List (High Evidence).
Gene: fpr2 has been classified as Amber List (Moderate Evidence).
gene: FPR2 was added gene: FPR2 was added to Viral susceptibility. Sources: Expert Review Red,ESID Registry 20171117 Mode of inheritance for gene: FPR2 was set to Unknown Phenotypes for gene: FPR2 were set to Localized juvenile peridontitis