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

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

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: jiangjiandong@imb.pumc.edu.cn.
  • 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: liyuhuan@imb.pumc.edu.cn.
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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