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heme oxygenase-1 agonist CoPP suppresses influenza virus replication through IRF3-mediated generation of IFN-α/β.

Abstract
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.
AuthorsLin-Lin Ma, Peng Zhang, Hui-Qiang Wang, Yan-Fei Li, Jin Hu, Jian-Dong Jiang, Yu-Huan Li
JournalVirology (Virology) Vol. 528 Pg. 80-88 (02 2019) ISSN: 1096-0341 [Electronic] United States
PMID30580124 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2018. Published by Elsevier Inc.
Chemical References
  • Enzyme Activators
  • Interferon Regulatory Factor-3
  • Interferon-alpha
  • Irf3 protein, mouse
  • Protoporphyrins
  • cobaltiprotoporphyrin
  • Interferon-beta
  • Heme Oxygenase-1
Topics
  • Animals
  • Dogs
  • Enzyme Activators (pharmacology)
  • Gene Expression Regulation (immunology)
  • Heme Oxygenase-1 (genetics, immunology)
  • Immunity, Innate
  • Influenza A virus (drug effects)
  • Interferon Regulatory Factor-3 (immunology)
  • Interferon-alpha (immunology)
  • Interferon-beta (immunology)
  • Madin Darby Canine Kidney Cells
  • Mice
  • Protoporphyrins (pharmacology)
  • RAW 264.7 Cells
  • Virus Replication (drug effects)

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