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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http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2893.2011.01480.x/abstract

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

expression of viral antigens: genotype B vs C

C.-J. Liu1,2,3, H.-R. Cheng1, C.-L. Chen1, T.-C. Chen1, T.-C. Tseng4, Z.-L.

Wang1, P.-J. Chen1,2,3,5, C.-H. Liu2, D.-S. Chen1,2,3, J.-H. Kao1,2,3,5

Article first published online: 4 JUL 2011

DOI: 10.1111/j.1365-2893.2011.01480.x

© 2011 Blackwell Publishing Ltd

Issue

Journal of Viral Hepatitis

Early View (Online Version of Record published before inclusion in an issue)

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.