Sequence Variation Upstream of Precore Translation Initiation Codon Reduces Hepatitis B Virus e Antigen Production

Sang Hoon Ahn, Anna Kramvis, Shigenobu Kawai, Hans Christian Spangenberg, Jisu Li, Gerald Kimbi, Michael Kew, Jack Wands, Shuping Tong

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)


Background & Aims: Most South African hepatitis B virus strains harbor point mutations immediately upstream of the precore AUG codon. The aim of this study was to determine their effect on hepatitis B e antigen expression. Methods: The hepatitis B virus DNA sequence around the precore region was determined from sera of 45 black South Africans. The South African mutations were introduced into hepatitis B virus dimers of the same genotype, and hepatitis B e antigen was quantified from culture medium of transfected HepG2 or Huh7 cells. Results: The South African sequence changes were easily detectable in the acute, hepatitis B e antigen-positive phase of infection, suggesting that they were stable traits and were not selected by immune pressure. Triple mutations at the -5, -3, and -2 positions of the AUG codon severely impaired hepatitis B e antigen expression (P < 0.001). The frequent double mutation at the -5 and -2 positions moderately reduced hepatitis B e antigen levels (P < 0.001) to an extent comparable to that of the common core promoter mutations (1762T1764A). The presence of both South African and core promoter mutations diminished hepatitis B e antigen expression in an additive manner. It is interesting to note that the triple South African mutations enabled core protein translation from precore messenger RNA, which could rescue the replication defect of a hepatitis B virus genome with an ablated core gene. Conclusions: We have identified a novel class of hepatitis B e antigen variants with reduced hepatitis B e antigen translation by a ribosomal leaky scanning mechanism. Reduction in hepatitis B e antigen expression may contribute to accelerated seroconversion from hepatitis B e antigen to its antibody in black South Africans infected with hepatitis B virus very early in life.

Original languageEnglish
Pages (from-to)1370-1378
Number of pages9
Issue number5
Publication statusPublished - 2003 Nov

Bibliographical note

Funding Information:
Supported by a grant from the Brain Korea 21 Project for Medical Science (to S.H.A.); Lifespan Research Funds; grants CA35711, AA20169, p20RR15578, R13 AI5224101, AI54535, and DK62857 from the National Institutes of Health; and Ernst-Jung-Stiftung, Hamburg, Germany. J.L. is a Liver Scholar from the American Liver Foundation.

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology


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