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Current Topics in Virology   Volumes    Volume 1 
Hepatitis B virus C-gene expression and function: the lessons learned from viral mutants
Victor E. Buckwold, Jing-hsiung Ou
Pages: 71 - 81
Number of pages: 11
Current Topics in Virology
Volume 1 

Copyright © 1999 Research Trends. All rights reserved


Hepatitis B virus (HBV) is a small DNA virus that can cause severe liver disease. The HBV C-gene produces a structural protein called core protein and a non-structural protein called precore protein which is the precursor of the e antigen (HBeAg) found in patients’ sera. C-gene mutations may affect the core protein, the precore protein or the basal core promoter (BCP). Core protein mutations often occur in its T-cell and B-cell epitopes indicating the results of immunoselection. Large internal deletions within the core coding sequence leading to a defective interfering-like phenotype may also be observed. Mutations that affect the precore protein frequently abolish its expression and appear to be selected for on the basis of sequence constraints imposed by the overlapping ε pregenomic RNA packaging signal, X protein and the primer binding site. These mutants often prevail over the wild- type virus during chronic infection, suggesting that they have a selective advantage. While the wild-type virus frequently leads to persistent infection following neonatal infection, the HBeAg-negative mutants do not. Thus, the precore gene plays both positive and negative roles in the HBV life cycle. The BCP also contains hotspots for mutations which can differentially affect precore and core gene expression. These mutations are selected for on the basis of overlapping requirements for the BCP and X protein. The phenotypes of these viral mutants provide valuable information to understand the molecular biology and the pathogenesis of this virus.

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