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

  • Virology. 2019 Feb;528:80-88. doi: 10.1016/j.virol.2018.11.016.
Lin-Lin Ma  1 ,  Peng Zhang  2 ,  Hui-Qiang Wang  2 ,  Yan-Fei Li  3 ,  Jin Hu  2 ,  Jian-Dong Jiang  4 ,  Yu-Huan Li  5
Affiliations
  • 1. Key Laboratory of Molecular Imaging of Shanghai Education Commission, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China; Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
  • 2. Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
  • 3. Key Laboratory of Molecular Imaging of Shanghai Education Commission, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China.
  • 4. Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: [email protected].
  • 5. Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: [email protected].
PMID: 30580124 DOI: 10.1016/j.virol.2018.11.016
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.

Keywords
CoPP; Heme oxygenase-1; IFN-α/β; IRF3; Influenza virus.
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