Dopamine Inhibits the Expression of Hepatitis B Virus Surface and e Antigens by Activating the JAK/STAT Pathway and Upregulating Interferon-stimulated Gene 15 Expression

Background and Aims:Hepatitis B virus(HBV)infection is a major risk factor for cirrhosis and liver cancer,and its treatment continues to be difficult.We previously demonstrated that a dopamine analog inhibited the packaging of pregenomic RNA into capsids.The present study aimed to determine the effect of dopamine on the expressions of hepatitis B virus surface and e antigens(HBsAg and HBeAg,respectively)and to elucidate the underlying mechanism.Methods:We used dopamine-treated HBVinfected HepG2.2.15 and NTCP-G2 cells to monitor HBsAg and HBeAg expression levels.We analyzed interferon-stimulated gene 15(ISG15)expression in dopamine-treated cells.We knocked down ISG15 and then monitored HBsAg and HBeAg expression levels.We analyzed the expression of Janus kinase(JAK)/signal transducer and activator of transcription(STAT)pathway factors in dopamine-treated cells.We used dopamine hydrochloride-treated adeno-associated virus/HBV-infected mouse model to evaluate HBV DNA,HBsAg,and HBeAg expression.HBV virus was collected from HepAD38.7 cell culture medium.Results:Dopamine inhibited HBsAg and HBeAg expression and upregulated ISG15 expression in HepG2.2.15 and HepG2-NTCP cell lines.ISG15 knockdown increased HBsAg and HBeAg expression in HepG2.2.15 cells.Dopamine-treated cells activated the JAK/STAT pathway,which upregulated ISG15 expression.In the adeno-associated virus-HBV murine infection model,dopamine downregulated HBsAg and HBeAg expression and activated the JAK-STAT/ISG15 axis.Conclusions:Dopamine inhibits the expression of HBsAg and HBeAg by activating the JAK/STAT pathway and upregulating ISG15 expression.