STAT3 Signaling Pathway Depressed HCV Infection

Hepatitis C virus(HCV)is one of the leading causes of severe liver diseases.Chronic HCV infection can lead to hepatocellular carcinoma(HCC).About four millions of new HCV case increased every year worldwide.In cases,HCV infection remains one of global public health burdens.In recent years,although direct-acting anti-disease drugs(DAA)can greatly increase the cure rate of HCV-infected patients,the treatment effect of HCV is still difficult due to widespread distribution,highly viral mutation rate,and drug resistance.Lack of HCV vaccine,drug-resistant mutations,and limitated mechanisms of HCV infection and pathegenesis,it is necessary to further study the mechanism of HCV infection.These studies could support the theoretical basic for protecting HCV infection and improving treatment rate.STAT3 signaling pathway plays an important role in HCC patients,and could influence the drug-resistant treatment effect in these patients.Thus,we suggested STAT3 signaling pathway might influence HCV infection.This study analyzed the expression of STAT3 pathway genes(IL6R,HNF1?,HNF4?,STAT3,MRP2)in HCV-infected cells at the cellular level.Then,the IL6 gene was overexpressed,the viral proliferation and infection were suppressed in HCV infected cells.Firstly,Huh7.5.1 cells were infected by using HCV,the viral load in the supernatant was detected.mRNA level of the HNF1? gene significantly increased at 24 h(P=0.027),48 h(P<0.0001),and 72 h(P<0.0001)after HCV infection.The mRNA level of the STAT3 gene also significantly increased at 24 h(P=0.001),48 h(P<0.0001)and 72 h(P=0.003))after HCV infection.The mRNA level of the IL6 R gene and the MRP2 gene significantly increased at 48 h(P<0.0001),respectively.The mRNA level of the HNF4? gene showed no change.However,the protein level of all six genes were increased by western blot.In order to investigate the effection of STAT3 signaling pathway in HCV infected cells,the IL6 gene was cloned and then it was transfected with Huh7.5.1 cells infected with HCV.Our results showed that viral load decreased at 24 h after infection.and the viral load was significantly less than that in controls.However,the viral load increased at 72 h after HCV infection.mRNA level of the HNF1? genesignificantly increased at 24 h(P=0.023)and 72 h(P=0.0004)after transfection.The mRNA expression of the STAT3 gene also significantly increased at 24 h(P=0.003),48 h(P=0.0015),and 72 h(P<0.0001)after transfection.The mRNA level of the IL6 R gene significantly increased at 24 h(P=0.027)and 72 h(P=0.007)after transfection.mRNA level of the MRP2 and HNF4? genes showed no change.Except for MRP2 protein,the proten level of HNF1?,HNF4?,STAT3,pSTAT3,IL6 R and IL6 protein showed time-dependently increased.In summary,HCV infection actived the STAT3 signaling pathway.The mRNA and protein level of this pathway increased after HCV infection.At the same time,the IL6 gene was overexpressed,we identified HCV proliferation was suppressed.Our results supported the theoretical basis for further understanding the pathegenic mechanisms of HCV infection and disease progression.