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

¹ Biomedicine Research Group, Korea Research Institute of Bioscience and Biotechnology, KIST, Taejon, 305-606
and² 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 +82 42 860 4593.

Received 23 October 1995; accepted 10 January 1996.

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