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Complete hepatitis B virus genome analysis in HBsAg positive mothers and their infants with fulminant hepatitis B.

Friedt M, Gerner P, Wintermeyer P, Wirth S - BMC Gastroenterol (2004)

Bottom Line: Nucleotide exchanges in the basic core promotor and precore region were identified in all cases.A heterogeneous virus population was detected in four mothers.HBeAg negative variants were the predominant population in all children, whereas these mutants could only be detected as subpopulations in four mothers.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pediatrics, University of Zurich, Steinwiesstr. 75, CH-8032 Zurich, Switzerland. mfriedt@web.de

ABSTRACT

Background: After perinatal transmission of hepatitis B virus, infants of anti-HBe positive HBsAg carrier mothers may develop fulminant hepatitis B. Previously it has been suggested, that fulminant hepatitis B in adults was associated with specific mutations in the HBV-genome. The aim of this study was to investigate, whether specific viral variants are associated with fulminant hepatitis B in young infants.

Methods: The complete HBV-genomes of five mothers and their infants with fulminant hepatitis were isolated from the sera, amplified and directly sequenced.

Results: Between 6 and 43 base pair exchanges between the HBV genomes of the infants and their mothers were identified. The mutations spread over the entire virus genome. Nucleotide exchanges in the basic core promotor and precore region were identified in all cases. A heterogeneous virus population was detected in four mothers.

Conclusions: Many new mutations were proved to emerge during fulminant hepatitis B in infants, who had been perinatally infected. HBeAg negative variants were the predominant population in all children, whereas these mutants could only be detected as subpopulations in four mothers. The data suggest that the selection of a specific HBeAg negative viral strain may be associated with the development of fulminant hepatitis B in children.

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Amino acid exchanges between mothers and their infants in comparison to the Reference Sequence. Amino acid positions are numbered from the start codon of each protein. Only amino acid exchanges from mothers (M1–M5) to their infants (1–5) are depicted, the reference sequence according to Galibert et al.(1979) is listed for comparison; a heterogeneous population according to the nucleotide sequence is shown in italics.* = stop ; met = start codon, **aa exchange prevents preS2 production.
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Figure 3: Amino acid exchanges between mothers and their infants in comparison to the Reference Sequence. Amino acid positions are numbered from the start codon of each protein. Only amino acid exchanges from mothers (M1–M5) to their infants (1–5) are depicted, the reference sequence according to Galibert et al.(1979) is listed for comparison; a heterogeneous population according to the nucleotide sequence is shown in italics.* = stop ; met = start codon, **aa exchange prevents preS2 production.

Mentions: Many of the mutations resulted in amino acid changes in one or two open reading frames (ORF) (Figure 3). A total of 114 amino acid subsitutions were observed (Figure 3). The pre-C /C gene had 9 and 14 amino acid changes. The HBeAg synthesis was abrogated in all infants due to a precore stop codon, whereas this stop codon was detected as a major HBV-population in only one mother. 11 of 14 core mutations were detected in known B- T-cell epitopes (Table 1). The arginin-rich region (aa 155–171) that is important for DNA binding was highly conserved in all 5 cases. Furthermore, the cystein residues in the pre-C/ C gene (aa 23 of pre-C and aa 48, 61, 107, 183 of C gene), which are important for secretion and antigenicity of the core antigen were also conserved.


Complete hepatitis B virus genome analysis in HBsAg positive mothers and their infants with fulminant hepatitis B.

Friedt M, Gerner P, Wintermeyer P, Wirth S - BMC Gastroenterol (2004)

Amino acid exchanges between mothers and their infants in comparison to the Reference Sequence. Amino acid positions are numbered from the start codon of each protein. Only amino acid exchanges from mothers (M1–M5) to their infants (1–5) are depicted, the reference sequence according to Galibert et al.(1979) is listed for comparison; a heterogeneous population according to the nucleotide sequence is shown in italics.* = stop ; met = start codon, **aa exchange prevents preS2 production.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC425580&req=5

Figure 3: Amino acid exchanges between mothers and their infants in comparison to the Reference Sequence. Amino acid positions are numbered from the start codon of each protein. Only amino acid exchanges from mothers (M1–M5) to their infants (1–5) are depicted, the reference sequence according to Galibert et al.(1979) is listed for comparison; a heterogeneous population according to the nucleotide sequence is shown in italics.* = stop ; met = start codon, **aa exchange prevents preS2 production.
Mentions: Many of the mutations resulted in amino acid changes in one or two open reading frames (ORF) (Figure 3). A total of 114 amino acid subsitutions were observed (Figure 3). The pre-C /C gene had 9 and 14 amino acid changes. The HBeAg synthesis was abrogated in all infants due to a precore stop codon, whereas this stop codon was detected as a major HBV-population in only one mother. 11 of 14 core mutations were detected in known B- T-cell epitopes (Table 1). The arginin-rich region (aa 155–171) that is important for DNA binding was highly conserved in all 5 cases. Furthermore, the cystein residues in the pre-C/ C gene (aa 23 of pre-C and aa 48, 61, 107, 183 of C gene), which are important for secretion and antigenicity of the core antigen were also conserved.

Bottom Line: Nucleotide exchanges in the basic core promotor and precore region were identified in all cases.A heterogeneous virus population was detected in four mothers.HBeAg negative variants were the predominant population in all children, whereas these mutants could only be detected as subpopulations in four mothers.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pediatrics, University of Zurich, Steinwiesstr. 75, CH-8032 Zurich, Switzerland. mfriedt@web.de

ABSTRACT

Background: After perinatal transmission of hepatitis B virus, infants of anti-HBe positive HBsAg carrier mothers may develop fulminant hepatitis B. Previously it has been suggested, that fulminant hepatitis B in adults was associated with specific mutations in the HBV-genome. The aim of this study was to investigate, whether specific viral variants are associated with fulminant hepatitis B in young infants.

Methods: The complete HBV-genomes of five mothers and their infants with fulminant hepatitis were isolated from the sera, amplified and directly sequenced.

Results: Between 6 and 43 base pair exchanges between the HBV genomes of the infants and their mothers were identified. The mutations spread over the entire virus genome. Nucleotide exchanges in the basic core promotor and precore region were identified in all cases. A heterogeneous virus population was detected in four mothers.

Conclusions: Many new mutations were proved to emerge during fulminant hepatitis B in infants, who had been perinatally infected. HBeAg negative variants were the predominant population in all children, whereas these mutants could only be detected as subpopulations in four mothers. The data suggest that the selection of a specific HBeAg negative viral strain may be associated with the development of fulminant hepatitis B in children.

Show MeSH
Related in: MedlinePlus