Effects of hepatitis B virus precore and basal core promoter mutations on the expression of viral antigens: genotype B vs C

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J Viral Hepat. 2011 Oct;18(10):e482-e490. doi: 10.1111/j.1365-2893.2011.01480.x.

Epub 2011 Jul 4.

Effects of hepatitis B virus precore and basal core promoter mutations on the

expression of viral antigens: genotype B vs C.

Liu CJ, Cheng HR, Chen CL, Chen TC, Tseng TC, Wang ZL, Chen PJ, Liu CH, Chen DS,

Kao JH.

Source

Graduate Institute of Clinical Medicine, National Taiwan University College of

Medicine and National Taiwan University Hospital, Taipei, Taiwan Department of

Internal Medicine, National Taiwan University College of Medicine and National

Taiwan University Hospital, Taipei, Taiwan Hepatitis Research Center, National

Taiwan University College of Medicine and National Taiwan University Hospital,

Taipei, Taiwan Department of Internal Medicine, Buddhist Tzu Chi General

Hospital Taipei Branch, Taipei, Taiwan Department of Medical Research, National

Taiwan University College of Medicine and National Taiwan University Hospital,

Taipei, Taiwan.

Abstract

Summary.  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.

© 2011 Blackwell Publishing Ltd.

PMID: 21914067 [PubMed - as supplied by publisher]