Mutations in the transcriptional regulatory region of the precore and core/pregenome of a hepatitis B virus with defective HBeAg production.
Termination mutations in the precore open reading frame of hepatitis B virus (HBV) variants with defective hepatitis B e antigen (HBeAg) production have been demonstrated in both infected patients who have seroconverted to anti-HBe and those with fulminant hepatitis B. A donated plasma sample was found to be positive for the hepatitis B surface antigen, but negative for both HBeAg and anti-HBe. The HBV DNA titer in the plasma was estimated to be 32 pg/ml, and circulating virus-like particles were observed by electron microscopy. The entire nucleotide sequence of the virus was determined and at least 7 nucleotides were found to be unique when compared with previously reported sequences. These nucleotides created no termination codon in the precore/core, pol, preS/S and HBx open reading frames. The deduced amino acid substitutions were 28 Arg--Gln, 94 His--Tyr, 131 Val--Ile and 132 Phe--Tyr of HBx and 715 Met--Val and 789 Asp--Asn of pol. Furthermore, the precore and core/pregenome promoter contained altered 1764 A, 1766 T and 1768 A. Therefore, mutations in regions other than the precore open reading frame can cause defective HBeAg production.
Moriyama
K
K
First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Takada
T
T
Tsutsumi
Y
Y
Fukada
K
K
Ishibashi
H
H
Niho
Y
Y
Maeda
Y
Y
D000328:Adult; D001483:Base Sequence; D003062:Codon; D004279:DNA, Viral; D005260:Female; D016679:Genome, Viral; D006513:Hepatitis B e Antigens; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D014158:Transcription, Genetic
D003062:Codon; D004279:DNA, Viral; D006513:Hepatitis B e Antigens