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Fish & shellfish immunology v.79, 2018년, pp.65 - 72  

Heme Oxygenase-1 inhibits spring viremia of carp virus replication through carbon monoxide mediated cyclic GMP/Protein kinase G signaling pathway

Li, Cong (Department of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China ) ; Li, Lijuan (Department of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China ) ; Jin, Ling (Department of Biomedical Science, Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR, 97330, United States ) ; Yuan, Junfa (Department of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China ) ;
  • 초록  

    Abstract Spring viremia of carp virus (SVCV) is the etiological agent of spring viremia of carp (SVC) and causes mass mortality in common carp ( Cyprinus carpio ). Currently, no effective treatments or commercial vaccines against SVCV are available. Heme oxygenase-1 (HO-1), an enzyme that catalyzes the degradation of heme to produce carbon monoxide (CO), biliverdin and ferrous iron (Fe 2+ ), exerts anti-oxidant, antiinflammatory and anti-apoptotic properties. Previous studies demonstrated that nuclear factor-erythroid 2 related factor 2 (Nrf2) functions as an important upstream regulator of HO-1 and exhibits robust activity against SVCV infection. In this study, we further examined the antiviral activity of HO-1 against SVCV infection. The elevated expression of HO-1 was induced upon cobalt protoporphyrin (CoPP) treatment in EPC cells without affecting cell viability and thus inhibited SVCV replication in a dose dependent manner. Knocking down of HO-1 rescued SVCV replication. Thereby, the antiviral activity of ROS/Nrf2/HO-1 axis was confirmed in EPC cells. Furthermore, HO-1 enzymatic products CO, but not biliverdin, markedly inhibited SVCV replication via the activation of cyclic GMP/protein kinase G signaling pathway. Collectively, these findings suggest potential drug or therapy that induced the Nrf2/HO-1/CO/cGMP/PKG signaling pathway as a promising strategy for treating SVC. Highlights The antiviral activity of ROS/Nrf2/HO-1 axis in aquatic animal cells was confirmed. HO-1 enzymatic products CO, but not biliverdin, inhibits SVCV replication. CO blocks SVCV infection via the activation of cyclic GMP/protein kinase G signaling pathway.


  • 주제어

    Spring viremia of carp virus .   Heme oxygenase-1 .   Carbon monoxide .   Biliverdin .   Antiviral.  

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