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.
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Authors | Lin-Lin Ma, Peng Zhang, Hui-Qiang Wang, Yan-Fei Li, Jin Hu, Jian-Dong Jiang, Yu-Huan Li |
Journal | Virology
(Virology)
Vol. 528
Pg. 80-88
(02 2019)
ISSN: 1096-0341 [Electronic] United States |
PMID | 30580124
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 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
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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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