Curcumin inhibits hepatitis B virus infection by downregulating ccc DNA-bound histone acetylation

AIM To investigate the potential effect of curcumin on hepatitis B virus(HBV) covalently closed circular DNA(ccc DNA) and the underlying mechanism.METHODS A Hep G2.2.15 cell line stably transfected with HBV was treated with curcumin, and HBV surface antigen(HBs Ag) and e antigen(HBe Ag) expression levels were assessed by ELISA. Intracellular HBV DNA replication intermediates and ccc DNA were detected by Southern blot and real-time PCR, respectively. The acetylation levels of histones H3 and H4 were measured by Western blot. H3/H4-bound ccc DNA was detected by chromatin immunoprecipitation(Ch IP) assays. The deacetylase inhibitors trichostatin A and sodium butyrate were used to study the mechanism of action for curcumin. Additionally, short interfering RNAs(si RNAs) targeting HBV were tested along with curcumin.RESULTS Curcumin treatment led to time-and dose-dependent reductions in HBs Ag and HBe Ag expression and significant reductions in intracellular HBV DNA replication intermediates and HBV ccc DNA. After treatment with 20 μmol/L curcumin for 2 d, HBs Ag and ccc DNA levels in Hep G2.2.15 cells were reduced by up to 57.7%(P < 0.01) and 75.5%(P < 0.01), respectively, compared with levels in non-treated cells. Meanwhile, time-and dose-dependent reductions in the histone H3 acetylation levels were also detected upon treatment with curcumin, accompanied by reductions in H3-and H4-bound ccc DNA. Furthermore, the deacetylase inhibitors trichostatin A and sodium butyrate could block the effects of curcumin. Additionally, transfection of si RNAs targeting HBV enhanced the inhibitory effects of curcumin.CONCLUSION Curcumin inhibits HBV gene replication via downregulation of ccc DNA-bound histone acetylation and has the potential to be developed as a ccc DNA-targeting antiviral agent for hepatitis B.

Dynamic changes of HBV DNA in serum and peripheral blood mononuclear cells of chronic hepatitis patients after lamivudine treatment

瞄准：在浆液和外部血学习肝炎 B (HBV ) DNA 的动态变化在 lamivudine 以后的病人的单音的原子房间(PBMC ) 治疗。方法：有长期的 HBV 感染的 72 个病人的一个总数在这研究被包括。所有病人被证实有下列条件：超过 16 岁，提高了浆液丙氨酸 aminotransferase (中高音) ，积极肝炎 B e 抗原(HBeAg ) ，在浆液和 PBMC 的积极 HBV DNA，对 HAV 的否定抗体， HCV， HDV， HEV。长期的肝损坏的另外的可能的原因酒精和自体免疫的疾病例如药，被排除。72 个盒子随机被划分成 lamivudine 治疗组(n = 42 ) 并且控制组(n = 30 ) 。HBV DNA 被荧光在浆液并且在 PBMC 检测量的聚合酶链反应(PCR ) ，在期间并且在 lamivudine 治疗以后。结果：在治疗组， HBV DNA 在 lamivudine 治疗的 48 wk 期间分别地从 42 个盒子在浆液并且在 PBMC 变得否定， 38 和 25，否定的率分别地是 90.5% 和 59.5% 。在控制组，否定的率分别地是 23.3% 和 16.7% 。它作为与控制组(P【0.005 ) 相比在 12， 24 和 48 wk 是统计上重要的。HBV DNA 的平均变换时期在 PBMC 在浆液和 16 wk (8-24 wk ) 是 6 wk (2-8 wk ) 。结论：Lamivudine 在浆液并且在 PBMC 在 HBV 复制上有显著禁止的效果。在 PBMC 的 HBV DNA 上的禁止的效果在浆液是比那弱的。