The Antiviral Mechamism Research Of Heme Oxygenase-1 Against Spring Viremia Of Carp Virus Replication

Heme oxygenase-1?HO-1?,an enzyme that catalyzes the degradation of heme to produce carbon monoxide?CO?,biliverdin and ferrous iron(Fe²⁺),exerts anti-oxidative,anti-inflammatory and anti-apoptotic properties.Recently,growing researches have showed that HO-1 can inhibit the replication of various viruses,such as Porcine Reproductive and Respiratory Syndrome Virus?PRSSV?,Hepatitis B Virus?HBV?,and Ebola Virus?EBOV?.However,the effect of HO-1 on SVCV replication still remains unknown.Spring viremia of carp virus?SVCV?is the etiological agent of spring viremia of carp?SVC?.Currently,no effective treatments or vaccines against SVCV infection are available.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.SVCV infection significantly down-regulates HO-1expression and knocking down HO-1 by specific HO-1 siRNA restores SVCV replication,which suggested that HO-1 and SVCV replication have close linkage.In this study,we further examined the antiviral activity and mechanism of HO-1against 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.CoPP inhibited SVCV infection at its relatively later stage.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.Overall,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.