Defects in the precore region of hepatitis B virus DNA in a plasma pool from carriers seropositive for antibody against e antigen and with infectivity in chimpanzees.
A plasma pool from 12 asymptomatic carriers seropositive for antibody against hepatitis B e antigen (anti-HBe) contained hepatitis B virus (HBV) with chimpanzee infectious doses of 1-100/mL, and another pool from 12 carriers positive for hepatitis B e antigen (HBeAg) contained 10(8)/mL doses or more. The HBeAg-positive pool contained 10(6)-fold more HBV DNA than the anti-HBe-positive pool, reflecting the difference in infectivity in chimpanzees. The precore region sequences of HBV DNA in the two plasma pools were amplified by polymerase chain reaction, and separate HBV DNA clones were propagated for determining the nucleotide sequence. Of 114 clones from the anti-HBe-positive pool, 113 displayed 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 the remaining clone had a point mutation from adenine to cytosine at the first letter of codon 1 (CTG) to inhibit the translation initiation of the precore region. Precore region defects, in contrast, were observed in only 10 (8%) of 119 clones from the HBeAg-positive pool. These results indicate the infectious capacity of HBV mutants, defective in the precore region and incapable of directing the synthesis and secretion of HBeAg, which prevail in the circulation of hosts after they seroconvert from HBeAg to anti-HBe.
Omi
S
S
Immunology Division, Fichi Medical School, Tochigi-Ken, Japan.
Okamoto
H
H
Tsuda
F
F
Mayumi
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000737:chemistry*; D006510:Hepatitis B Antibodies / Q000276:immunology*; D006513:Hepatitis B e Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D016133:Polymerase Chain Reaction
D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens