tetano
Editor, Senior Moderator
Virology. 2018 Dec 20;528:80-88. doi: 10.1016/j.virol.2018.11.016. [Epub ahead of print]
[h=1]heme oxygenase-1 agonist CoPP suppresses influenza virus replication through IRF3-mediated generation of IFN-α/β.[/h] Ma LL[SUP]1[/SUP], Zhang P[SUP]2[/SUP], Wang HQ[SUP]2[/SUP], Li YF[SUP]3[/SUP], Hu J[SUP]2[/SUP], Jiang JD[SUP]4[/SUP], Li YH[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The innate immunity plays an essential role in defending infection of Influenza A virus (IAV). The regulatory effect of heme oxygenase-1 (HO-1), a cytoprotective enzyme, on innate immunity has been revealed. In this study, we aim to confirm the antiviral effect of CoPP (Cobaltic Protoporphyrin IX Chloride), a potent HO-1 inducer on IAV infection and elucidate the possible mechanism of HO-1-mediated host innate immune responses. Our results show that CoPP exhibits broad-spectrum antiviral activities against IAV. Furthermore, CoPP attenuates IAV replication through inducing type I IFNs response, not depending on HO-1 enzymatic activity. We also provide direct evidence that HO-1-mediated type I IFN response activation is largely due to its interaction with IRF3, which then promotes IRF3 phosphorylation and nuclear translocation. These results suggest that HO-1 agonist CoPP suppresses IAV replication through IRF3-mediated generation of IFN-α/β. Thus, therapeutic induction of HO-1 might be a promising strategy to combat IAV epidemics.
[h=4]KEYWORDS:[/h] CoPP; Heme oxygenase-1; IFN-α/β; IRF3; Influenza virus
PMID: 30580124 DOI: 10.1016/j.virol.2018.11.016
[h=1]heme oxygenase-1 agonist CoPP suppresses influenza virus replication through IRF3-mediated generation of IFN-α/β.[/h] Ma LL[SUP]1[/SUP], Zhang P[SUP]2[/SUP], Wang HQ[SUP]2[/SUP], Li YF[SUP]3[/SUP], Hu J[SUP]2[/SUP], Jiang JD[SUP]4[/SUP], Li YH[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The innate immunity plays an essential role in defending infection of Influenza A virus (IAV). The regulatory effect of heme oxygenase-1 (HO-1), a cytoprotective enzyme, on innate immunity has been revealed. In this study, we aim to confirm the antiviral effect of CoPP (Cobaltic Protoporphyrin IX Chloride), a potent HO-1 inducer on IAV infection and elucidate the possible mechanism of HO-1-mediated host innate immune responses. Our results show that CoPP exhibits broad-spectrum antiviral activities against IAV. Furthermore, CoPP attenuates IAV replication through inducing type I IFNs response, not depending on HO-1 enzymatic activity. We also provide direct evidence that HO-1-mediated type I IFN response activation is largely due to its interaction with IRF3, which then promotes IRF3 phosphorylation and nuclear translocation. These results suggest that HO-1 agonist CoPP suppresses IAV replication through IRF3-mediated generation of IFN-α/β. Thus, therapeutic induction of HO-1 might be a promising strategy to combat IAV epidemics.
[h=4]KEYWORDS:[/h] CoPP; Heme oxygenase-1; IFN-α/β; IRF3; Influenza virus
PMID: 30580124 DOI: 10.1016/j.virol.2018.11.016