tetano
Editor, Senior Moderator
J Infect Dis. 2016 Mar 30. pii: jiw127. [Epub ahead of print]
[h=1]Formyl peptide receptor 2 plays a deleterious role during influenza A virus infections.[/h] Tcherniuk S[SUP]1[/SUP], Cenac N[SUP]2[/SUP], Comte M[SUP]3[/SUP], Frouard J[SUP]3[/SUP], Errazuriz-Cerda E[SUP]4[/SUP], Galabov A[SUP]5[/SUP], Morange PE[SUP]1[/SUP], Vergnolle N[SUP]2[/SUP], Si-Tahar M[SUP]6[/SUP], Alessi MC[SUP]1[/SUP], Riteau B[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] Pathogenesis of influenza A virus (IAV) infections is a multifactorial process including 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.
[h=4]METHODS:[/h] We used pharmacologic approaches to investigate the role of FPR2 during influenza A virus infectionin vitroandin vivo RESULTS: In vitro, FPR2 expressed on A549 cells was activated by IAV which harbor its ligand Annexin-A1 in their 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-NH[SUB]2[/SUB]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 the deleterious role of FPR2 also occurs through an ERK-dependent pathway,in vivo In contrast, administration of the FPR2 antagonist WRW4 protected mice from lethal IAV infections.
[h=4]CONCLUSION:[/h] 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.
? The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.
PMID: 27034344 [PubMed - as supplied by publisher]
[h=1]Formyl peptide receptor 2 plays a deleterious role during influenza A virus infections.[/h] Tcherniuk S[SUP]1[/SUP], Cenac N[SUP]2[/SUP], Comte M[SUP]3[/SUP], Frouard J[SUP]3[/SUP], Errazuriz-Cerda E[SUP]4[/SUP], Galabov A[SUP]5[/SUP], Morange PE[SUP]1[/SUP], Vergnolle N[SUP]2[/SUP], Si-Tahar M[SUP]6[/SUP], Alessi MC[SUP]1[/SUP], Riteau B[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] Pathogenesis of influenza A virus (IAV) infections is a multifactorial process including 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.
[h=4]METHODS:[/h] We used pharmacologic approaches to investigate the role of FPR2 during influenza A virus infectionin vitroandin vivo RESULTS: In vitro, FPR2 expressed on A549 cells was activated by IAV which harbor its ligand Annexin-A1 in their 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-NH[SUB]2[/SUB]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 the deleterious role of FPR2 also occurs through an ERK-dependent pathway,in vivo In contrast, administration of the FPR2 antagonist WRW4 protected mice from lethal IAV infections.
[h=4]CONCLUSION:[/h] 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.
? The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.
PMID: 27034344 [PubMed - as supplied by publisher]