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.
First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
K
K
Moriyama
T
T
Takada
Y
Y
Tsutsumi
K
K
Fukada
H
H
Ishibashi
Y
Y
Niho
Y
Y
Maeda
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