Fulminant hepatitis B: induction by hepatitis B virus mutants defective in the precore region and incapable of encoding e antigen.
Clones of hepatitis B virus were propagated from 10 cases of fulminant hepatitis B after amplification by polymerase chain reaction and their nucleotide sequences of the precore region were determined. All 113 clones from 9 cases had a point mutation from guanine to adenine at nucleotide 83 in the precore region, which converted codon 28 for tryptophan (TGG) to a stop codon (TAG) and prohibited the synthesis and secretion of hepatitis B e antigen. Precore-region defects were not detected in any of 23 clones from the remaining 1 case. By contrast, precore-region defects were not found in any of 180 clones from 8 cases of acute hepatitis B without hepatic failure serving as controls. The source of infection was traceable in 3 cases. The same precore-region defect, along with the sequence identity of 435 nucleotides, was observed in clones from the case of a baby and his grandmother, who carried the virus and was implicated in the transmission, and also in clones from two pediatricians and the carrier patients they attended. These findings support the hypothesis that precore-defective mutants have stronger activity to induce fulminant hepatitis than nondefective viruses.
Kosaka
Y
Y
Department of Clinical Laboratory Medicine, School of Medicine, Mie University.
Takase
K
K
Kojima
M
M
Shimizu
M
M
Inoue
K
K
Yoshiba
M
M
Tanaka
S
S
Akahane
Y
Y
Okamoto
H
H
Tsuda
F
F
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006501:Hepatic Encephalopathy / Q000382:microbiology*; D006509:Hepatitis B / Q000382:microbiology* / Q000635:transmission; D006510:Hepatitis B Antibodies / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation
D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens