Novel pre-C/C gene mutants of hepatitis B virus in chronic active hepatitis: naturally occurring escape mutants

• Published in: Journal of general virology Vol. 77; no. 6; pp. 1129 - 1138
• Main Authors: Lee, Young Ik, Hur, Gang Min, Suh, Dong-Jin, Kim, Sun Hee
• Format: Journal Article
• Language: English
• Published: England Soc General Microbiol 01-06-1996
• Subjects: Adolescent; Adult; Amino Acid Sequence; Base Sequence; Chronic Disease; Codon; DNA Primers; DNA, Viral - blood; DNA, Viral - isolation & purification; Female; Genes, Viral; Genome, Viral; Hepatitis B - pathology; Hepatitis B - virology; hepatitis B virus; Hepatitis B virus - genetics; Hepatitis B virus - isolation & purification; Humans; Liver - pathology; Male; Middle Aged; Molecular Sequence Data; Open Reading Frames; Point Mutation; Polymerase Chain Reaction - methods; Sequence Deletion; Viral Core Proteins - biosynthesis
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/0022-1317-77-6-1129

1 Biomedicine Research Group, Korea Research Institute of Bioscience and Biotechnology, KIST, Taejon, 305-606
and 2 Department of Internal Medicine, College of Medicine, Ulsan University, Korea
We have analysed serum samples taken from hepatitis B virus (HBV) e antigen (HBeAg)-positive and HBeAg-negative chronic active hepatitis (CAH) patients by PCR using primers spanning the pre-core/core (C) and pre-S1/S2 ORFs. Nucleotide sequence analysis showed that among 18 HBV-infected CAH patients, 11 had virus with a G to A mutation (nucleotide 1896; leading to the formation of a stop codon) and one patient also had virus with an additional G to A mutation three nucleotides downstream (nucleotide 1899). HBV from three patients that were HBeAg-negative showed a 1 bp deletion at nucleotide 1937, causing pre-termination of the C gene. Mutation frequencies in the sequences identified as coding for cytotoxic T lymphocyte epitopes, B cell epitopes, CD4 + helper T cell epitopes and arginine-rich regions of the HBV C peptide were investigated. Mutations were more frequently identified in these regions, suggesting that the mutations might have been selected as a result of immune responses.
* Author for correspondence. Fax [phone].
Received 23 October 1995;
accepted 10 January 1996.