| Chronic hepatitis B is a major infectious disease caused by the continuous infection of Hepatitis B virus(HBV),and will eventually lead to major malignant diseases such as liver cirrhosis and liver cancer.However,due to the specificity of the hepatitis B virus to the host and the precise regulation of its life cycle,the ccc DNA of the HBV genome cannot be completely eliminated in the patient.Therefore,the current treatment of chronic hepatitis B cannot achieve a cure.At present,drugs for hepatitis B virus,such as interferon-α(IFN-α),have poor therapeutic effects and are prone to drug resistance.Therefore,exploring the mechanism of persistent HBV infection can provide a theoretical basis and target for the clinical treatment of chronic hepatitis B and drug development.Niacin is a type of vitamin B3 and is one of the 13 essential vitamins for the human body.Studies have found that infants liver cells niacin deficiency,more than95% of the HBV infection in infants and young children may induce the occurrence of chronic hepatitis B.According to existing studies,it is speculated that the occurrence of chronic hepatitis B may be closely related to the intake of niacin.Therefore,exploring the relationship between niacin and chronic hepatitis B will help us understand the function of vitamin B3 and its role in the occurrence of chronic hepatitis B(CHB),and find new targets for the treatment of CHB.This paper discusses the regulation of HBV infection by niacin.First,different concentrations of niacin were used to treat HLCZ01 cells infected with HBV for a long time.It was found that ccc DNA,Total DNA and pg RNA of HBV increased with the increase of niacin concentration after three days of treatment.However,the intracellular HBV-S antigen,HBV-Core protein,extracellular HBV-S antigen and extracellular HBV-DNA are all reduced.In order to rule out cell specificity,similar results were obtained in Hep G2.2.15 cells that can support HBV replication,suggesting that niacin can inhibit the expression of HBV virus-related proteins,allowing the accumulation of HBV nucleic acid in cells,thereby inhibiting HBV mature virus release of particles.In order to further explore the mechanism of niacin to regulate HBV infection,in HLCZ01 with HBV long-term infected and Hep G2.2.15 cells treated with different concentrations of niacin,it was found that the expression level of inflammatory cytokine TNF-α increased.Studies have shown that Toll-like receptors(TLR)can activate the MAPK signaling pathway after recognizing HBV,and can initiate the expression of downstream inflammatory factors such as TNF-α.We speculate that niacin can induce TNF-α expression by activating the MAPK signaling pathway.The results showed that niacin treatment resulted in a significant up-regulation of the phosphorylation levels of ERK1/2 and P38.In order to explore the long-term effects of niacin,in HLCZ01 cells long-term infected with HBV,long-term treatment with niacin can ultimately reduce the levels of HBV ccc DNA,Total DNA and pg RNA,as well as significantly reduce the expression levels of HBV-S antigen and HBV-Core protein.These results further verified the effect of niacin on HBV infection and revealed the use of niacin as a treatment for chronic hepatitis B.In summary,niacin reduced expression level of intracellular HBV-S antigen and HBV-Core protein,inhibiting the release of mature viral particles,so that the intracellular HBV ccc DNA,Total DNA and other HBV pg RNA viral nucleic acid occurs accumulation.It further promotes the phosphorylation of ERK1/2 and P38 in the MAPK signaling pathway,and then enhances the production of inflammatory cytokine TNF-α,which the levels of intracellular HBV-S antigen,Core protein and HBV genetic material ccc DNA,as well as Total DNA and pg RNA levels were significantly down-regulated,thereby achieving a significant long-term inhibition of chronic viral infections.It provides a new target and a theoretical basis for drug development for the treatment of chronic hepatitis B. |
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