Analysis of the precore DNA sequence and detection of precore antigen in liver specimens from patients with anti-hepatitis B e-positive chronic hepatitis.
A number of naturally occurring hepatitis B virus (HBV) mutants unable to synthesize the hepatitis B e antigen (HBeAg) have been identified in patients characterized by HBV DNA and anti-HBe in their serum. Because the analysis of the HBV-associated DNA and antigens in the liver tissue is still not complete, we investigated the precore sequence of HBV DNA and its encoded proteins in the liver tissue of 32 patients positive for HBV DNA and anti-HBe in their serum. Three different groups of patients were identified. Group I (n = 14) was characterized by viral DNA sequences with a G-A transition in the distal precore gene region, thus creating a termination codon (TAG). Liver tissue from this group was negative for HBeAg but positive for hepatitis B core antigen (HBcAg) and a peptide containing the last 10 aminoacids of the precore and the first four aminoacids of the c region. Group II (n = 6) showed variable mutations in base sequences further upstream and negative for HBeAg and the precore peptide. Group III (n = 12) contained wild-type HBV DNA sequences in the tissue and positivity for precore- and core-encoded proteins. We conclude from our study that the group of patients with HBV DNA and anti-HBe in the serum is rather heterogeneous, including HBV DNA mutations in the precore region as well as infection with the wild-type virus being negative for HBeAg in the serum. The precore peptide is produced and expressed in the tissue even when the formation of a stop codon at base 1896 prevents the complete translation of the entire HBe protein.
Dienes
H P
HP
Institute of Pathology, University of Mainz, Germany.
Gerken
G
G
Goergen
B
B
Heermann
K
K
Gerlich
W
W
Meyer zum Büschenfelde
K H
KH
D001483:Base Sequence; D002908:Chronic Disease; D004279:DNA, Viral / Q000235:genetics*; D006508:Hepatitis Antibodies / Q000032:analysis*; D006509:Hepatitis B / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D006512:Hepatitis B Core Antigens / Q000032:analysis / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000276:immunology* / Q000473:pathology; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data
D004279:DNA, Viral; D006508:Hepatitis Antibodies; D006512:Hepatitis B Core Antigens; D015335:Molecular Probes