Novel pre-C/C gene mutants of hepatitis B virus in chronic active hepatitis: naturally occurring escape mutants.
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.
Lee
Y I
YI
Biomedicine Research Group, Korea Research Institute of Bioscience and Biotechnology, KIST, Taejon, Korea.
Hur
G M
GM
Suh
D J
DJ
Kim
S H
SH
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002908:Chronic Disease; D003062:Codon; D017931:DNA Primers; D004279:DNA, Viral / Q000097:blood* / Q000302:isolation & purification; D005260:Female; D005814:Genes, Viral; D016679:Genome, Viral; D006509:Hepatitis B / Q000473:pathology / Q000821:virology*; D006515:Hepatitis B virus / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D017384:Sequence Deletion; D014758:Viral Core Proteins / Q000096:biosynthesis*
D003062:Codon; D017931:DNA Primers; D004279:DNA, Viral; D014758:Viral Core Proteins