期刊
JOURNAL OF VIRAL HEPATITIS
卷 18, 期 10, 页码 E482-E490出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1365-2893.2011.01480.x
关键词
antigen; basal core promoter; expression; genotype; mutation; precore
资金
- National Taiwan University Hospital
- National Science Council
- Department of Health, Executive Yuan, Taiwan
- National Taiwan University, Taiwan
- Liver Disease Prevention and Treatment Research Foundation, Taiwan
Hepatitis B virus (HBV) genotypes/mutants are known to affect natural outcomes. The virologic differences among HBV genotype, precore and basal core promoter (BCP) mutations were investigated. HBV strains were isolated from 18 hepatitis B e antigen (HBeAg)-positive patients (nine genotype B and nine genotype C). All had precore and BCP wild-type sequences. After cloning of full-length HBV genome, the effects of viral genotype, precore and BCP mutations singly or additively on the expression of viral DNA and antigens were investigated by mutagenesis and transfection assays in Huh7 cells. Significant findings included the following: (i) expression of intracellular core protein increased when precore or BCP mutation was introduced in genotype C strains; (ii) expression of intracellular surface protein was lower in genotype C precore wild-type strain compared with genotype B; (iii) precore mutation was associated with a lower extracellular expression level of HBV DNA; (iv) secretion of hepatitis B surface antigen in genotype C was lower than that in genotype B; and (v) secretion of HBeAg in genotype B was lower than that in genotype C. No additive effect was observed by combining precore and BCP mutations. Hence, HBV genotype and precore/BCP mutations correlate with intrahepatic expression of viral antigens in vitro.
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