Mutation preventing formation of hepatitis B e antigen in patients with chronic hepatitis B infection.
Some patients with chronic hepatitis B virus (HBV) infection are HB e antigen (HBeAg) negative, have circulating HBV particles, and often have especially severe chronic hepatitis. To test the hypothesis that the absence of HBeAg production may be due to a change in the nucleotide sequence of the pre-core region of the genome, 18 Greek and 3 non-Greek patients positive for HB surface antigen underwent direct sequencing of HBV-DNA amplified from sera. In 7 out of 8 HBeAg negative patients, two mutations (guanosine to adenosine) were found in the terminal two codons of the pre-core region, giving the sequence TAGGACATG. The remaining patient had the first mutation only. The sequence TGGGGCATG was found in 4 of 5 of the HBeAg positive patients. The first mutation results in a translational stop codon that is predicted to result in failure to produce HBeAg. The rest of the pre-core region in the HBeAg negative patients was otherwise homologous to that of the HBeAg positive patients and to known sequences.
Carman
W F
WF
Department of Medicine, St Mary's Hospital Medical School, London.
Jacyna
M R
MR
Hadziyannis
S
S
Karayiannis
P
P
McGarvey
M J
MJ
Makris
A
A
Thomas
H C
HC
D000595:Amino Acid Sequence; D001483:Base Sequence; D003062:Codon / Q000235:genetics; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics*; D005784:Gene Amplification; D006115:Greece; D006509:Hepatitis B / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D006510:Hepatitis B Antibodies / Q000032:analysis; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006513:Hepatitis B e Antigens / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000502:physiology*; D006521:Hepatitis, Chronic / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D014176:Protein Biosynthesis
D003062:Codon; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens