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The Annexin A1 Receptor FPR2 Regulates the Endosomal Export of Influenza Virus

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 w...

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Autores principales: Rahman, Fryad, Chebbo, Mohammad, Courtin, Noémie, Fotso Fotso, Aurelien, Alessi, Marie-Christine, Riteau, Béatrice
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983815/
https://www.ncbi.nlm.nih.gov/pubmed/29738458
http://dx.doi.org/10.3390/ijms19051400
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author Rahman, Fryad
Chebbo, Mohammad
Courtin, Noémie
Fotso Fotso, Aurelien
Alessi, Marie-Christine
Riteau, Béatrice
author_facet Rahman, Fryad
Chebbo, Mohammad
Courtin, Noémie
Fotso Fotso, Aurelien
Alessi, Marie-Christine
Riteau, Béatrice
author_sort Rahman, Fryad
collection PubMed
description 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.
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spelling pubmed-59838152018-06-05 The Annexin A1 Receptor FPR2 Regulates the Endosomal Export of Influenza Virus Rahman, Fryad Chebbo, Mohammad Courtin, Noémie Fotso Fotso, Aurelien Alessi, Marie-Christine Riteau, Béatrice Int J Mol Sci Article 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. MDPI 2018-05-08 /pmc/articles/PMC5983815/ /pubmed/29738458 http://dx.doi.org/10.3390/ijms19051400 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rahman, Fryad
Chebbo, Mohammad
Courtin, Noémie
Fotso Fotso, Aurelien
Alessi, Marie-Christine
Riteau, Béatrice
The Annexin A1 Receptor FPR2 Regulates the Endosomal Export of Influenza Virus
title The Annexin A1 Receptor FPR2 Regulates the Endosomal Export of Influenza Virus
title_full The Annexin A1 Receptor FPR2 Regulates the Endosomal Export of Influenza Virus
title_fullStr The Annexin A1 Receptor FPR2 Regulates the Endosomal Export of Influenza Virus
title_full_unstemmed The Annexin A1 Receptor FPR2 Regulates the Endosomal Export of Influenza Virus
title_short The Annexin A1 Receptor FPR2 Regulates the Endosomal Export of Influenza Virus
title_sort annexin a1 receptor fpr2 regulates the endosomal export of influenza virus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983815/
https://www.ncbi.nlm.nih.gov/pubmed/29738458
http://dx.doi.org/10.3390/ijms19051400
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