Fulminant hepatitis related to transmission of hepatitis B variants with precore mutations between spouses.
A precore defective variant of hepatitis B virus has been indicated to cause fulminant hepatitis in various instances such as intrahospital outbreaks or mother-to-child transmission of hepatitis B virus. To learn whether similar variants are involved in interspouse transmission, we analyzed three cases of fulminant hepatitis B that developed in formerly healthy subjects whose only exposure to hepatitis B virus was contact with their longtime spouses, who were carriers of HBV and positive for antibody to HBe. The DNA clones for precore and S genes were propagated from patients and spouses and sequenced. Because of the conservation of S-gene sequences and the identity of subtypes between patient and spouse, it was suggested that patients were infected with hepatitis B virus from their spouses, not from other sources. A TGG-to-TAG mutation at the 28th codon of the precore gene of hepatitis B virus was commonly observed in all DNA clones from patients with fulminant hepatitis and from their spouses. A 29th-codon GGC-to-GAC mutation was additionally evident in DNAs from one patient-and-spouse couple. A significant rise in the circulating hepatitis B virus concentration was transiently observed in the index spouse of this case just before development of fulminant hepatitis in her husband. The increase in circulating HBV DNA was associated with a rise in abundancy of variants with mutations at both the 28th and 29th codons, compared with variants with only a 28th-codon mutation. The double mutation in hepatitis B virus DNA may either help the virus escape immune surveillance or replicate at a higher rate than before.
Yotsumoto
S
S
Immunology Division, Jichi Medical School, Tochigi-ken, Japan.
Kojima
M
M
Shoji
I
I
Yamamoto
K
K
Okamoto
H
H
Mishiro
S
S
D001483:Base Sequence; D003001:Cloning, Molecular; D003062:Codon / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics*; D003673:Defective Viruses / Q000235:genetics* / Q000472:pathogenicity; D005260:Female; D005814:Genes, Viral; D014644:Genetic Variation; D005838:Genotype; D006509:Hepatitis B / Q000503:physiopathology / Q000635:transmission*; D006512:Hepatitis B Core Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009679:Nuclear Family; D009838:Oligodeoxyribonucleotides
D003062:Codon; D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D009838:Oligodeoxyribonucleotides