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Sodium selenite suppresses hepatitis B virus transcription and replication in human hepatoma cell lines.

ABSTRACT: Hepatitis B virus (HBV) infection is one of the most serious and prevalent health problems worldwide. Current anti-HBV medications have a number of drawbacks, such as adverse effects and drug resistance; thus, novel potential anti-HBV reagents are needed. Selenium (Se) has been shown to be involved in both human immunodeficiency virus and hepatitis C virus infections, but its role in HBV infection remains unclear. To address this, sodium selenite (Na2SeO3 ) was applied to three HBV cell models: HepG2.2.15 cells, and HuH-7 cells transfected with either 1.1 or 1.3× HBV plasmids. Cytotoxicity of Na2SeO3 was examined by Cell Counting Kit-8. Levels of viral antigen expression, transcripts, and encapsidated viral DNA were measured by enzyme-linked immunosorbent assay, northern blot, and Southern blot, respectively. There was no obvious cytotoxicity in either HepG2.2.15 or HuH-7 cells with <2.5 µM Na2SeO3 . Below this concentration, Na2SeO3 suppressed HBsAg and HBeAg production, HBV transcript level, and amount of genomic DNA in all three tested models, and suppression level was enhanced in line with increases in Na2 SeO3 concentration or treatment time. Moreover, the inhibitory effect of Na2SeO3 on HBV replication can be further enhanced by combined treatment with lamivudine, entecavir, or adefovir. Thus, the present study clearly proves that Na2SeO3 suppresses HBV protein expression, transcription, and genome replication in hepatoma cell models in a dose- and time-dependent manner.

SUBMITTER: Cheng Z

PROVIDER: S-EPMC7167125 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Hepatitis B virus efficiently infects non-adherent hepatoma cells via human sodium taurocholate cotransporting polypeptide.

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2013-06-05 | GSE41737 | GEO

Antiviral Activity of Chitosan Nanoparticles Encapsulating Curcumin Against Hepatitis C Virus Genotype 4a in Human Hepatoma Cell Lines.

Project description:Purpose:Current direct-acting antiviral agents for treatment of hepatitis C virus genotype 4a (HCV-4a) have been reported to cause adverse effects, and therefore less toxic antivirals are needed. This study investigated the role of curcumin chitosan (CuCs) nanocomposite as a potential anti-HCV-4a agent in human hepatoma cells Huh7. Methods:Docking of curcumin and CuCs nanocomposite and binding energy calculations were carried out. Chitosan nanoparticles (CsNPs) and CuCs nanocomposite were prepared with an ionic gelation method and characterized with TEM, zeta size and potential, and HPLC to calculate encapsulation efficiency. Cytotoxicity studies were performed on Huh7 cells using MTT assay and confirmed with cellular and molecular assays. Anti-HCV-4a activity was determined using real-time PCR and Western blot. Results:The strength of binding interactions between protein ligand complexes gave scores with NS3 protease, NS5A polymerase, and NS5B polymerase of -124.91, -159.02, and -129.16, for curcumin respectively, and -68.51, -54.52, and -157.63 for CuCs nanocomposite, respectively. CuCs nanocomposite was prepared at sizes 29-39.5 nm and charges of 33 mV. HPLC detected 4% of curcumin encapsulated into CsNPs. IC50 was 8 µg/mL for curcumin and 25 µg/mL for the nanocomposite on Huh7 but was 25.8 µg/mL and 34 µg/mL on WISH cells. CsNPs had no cytotoxic effect on tested cell lines. Apoptotic genes' expression revealed the caspase-dependent pathway mechanism. CsNPs and CuCs nanocomposite demonstrated 100% inhibition of viral entry and replication, which was confirmed with HCV core protein expression. Conclusion:CuCs nanocomposite inhibited HCV-4a entry and replication compared to curcumin alone, suggesting its potential role as an effective therapeutic agent.

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2013-06-05 | E-GEOD-41737 | biostudies-arrayexpress

Hepatitis C virus replication and Golgi function in brefeldin a-resistant hepatoma-derived cells.

Project description:Recent reports indicate that the replication of hepatitis C virus (HCV) depends on the GBF1-Arf1-COP-I pathway. We generated Huh-7-derived cell lines resistant to brefeldin A (BFA), which is an inhibitor of this pathway. The resistant cell lines could be sorted into two phenotypes regarding BFA-induced toxicity, inhibition of albumin secretion, and inhibition of HCV infection. Two cell lines were more than 100 times more resistant to BFA than the parental Huh-7 cells in these 3 assays. This resistant phenotype was correlated with the presence of a point mutation in the Sec7 domain of GBF1, which is known to impair the binding of BFA. Surprisingly, the morphology of the cis-Golgi of these cells remained sensitive to BFA at concentrations of the drug that allowed albumin secretion, indicating a dichotomy between the phenotypes of secretion and Golgi morphology. Cells of the second group were about 10 times more resistant than parental Huh-7 cells to the BFA-induced toxicity. The EC50 for albumin secretion was only 1.5-1.8 fold higher in these cells than in Huh-7 cells. However their level of secretion in the presence of inhibitory doses of BFA was 5 to 15 times higher. Despite this partially effective secretory pathway in the presence of BFA, the HCV infection was almost as sensitive to BFA as in Huh-7 cells. This suggests that the function of GBF1 in HCV replication does not simply reflect its role of regulator of the secretory pathway of the host cell. Thus, our results confirm the involvement of GBF1 in HCV replication, and suggest that GBF1 might fulfill another function, in addition to the regulation of the secretory pathway, during HCV replication.

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