Nucleic acid sequence analysis of the precore region of hepatitis B virus from sera of southern African black adult carriers of the virus.
Our purpose was to ascertain if mutations of the precore region of the hepatitis B virus genome, in particular the 1896 stop codon mutation, are responsible for the 95% hepatitis B e antigen (HBeAg)-negativity rate in southern African black adult carriers. Hepatitis B virus (HBV) DNA was extracted from the serum of 57 asymptomatic carriers (42 HBeAg-negative; 15 HBeAg-positive), the precore region was amplified using the polymerase chain reaction (PCR), and sequenced. Six carriers (14.6%) had mutations known to prevent HBeAg synthesis: 4 involved the precore initiation codon (1814), and one created a stop codon at 1874. The 1896 mutation occurred alone in one carrier only (2.4%). The infrequency of the 1896 mutation can be explained by the high prevalence (70%) of the adw subtype in the carriers studied. Inter alia, adw differs from ayw in that codon 15 is comprised of CCC instead of CCT. The presence of C instead of T in position 1858 precludes the G-to-A mutation at 1896 because the coexistence of these two mutations would destabilize the stem-loop structure of the RNA encapsidation signal, a finding confirmed by our observation that the CCC polymorphism and the 1896 mutation were mutually exclusive. Ten HBeAg-negative carriers (24%) had a missense mutation at position 1862 in the bulge of the RNA encapsidation signal, which may possibly affect HBeAg expression by interfering with either priming of reverse transcription or signal peptide cleavage. We conclude that the 1896 stop codon mutation accounts for a minority only of HBeAg-negative black carriers. A missense mutation in the bulge of the encapsidation signal may contribute to HBeAg negativity.
Kramvis
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A
Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa.
Bukofzer
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Kew
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MC
Song
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D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002353:Carrier State / Q000821:virology*; D004279:DNA, Viral / Q000097:blood / Q000737:chemistry*; D006509:Hepatitis B / Q000821:virology*; D006513:Hepatitis B e Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D014766:Viremia / Q000821:virology*
D004279:DNA, Viral; D006513:Hepatitis B e Antigens