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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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Related in: MedlinePlus

Mutations identified in the HBV genomes from mothers and infants are illustrated. (C)The horizontal line represents the HBV nucleotide sequence of the reference genome (11). (A) The four open reading frames (ORF) are depicted in open bars. Lines within these bars represent mutations resulting in amino acid changes in the infant with fulminant disease. (B) Black bars in the middle indicate enhancer and promotor regions (GRE: Glucocorticoid response element, ENH I-XP: enhancer I and X promotor, ENH II-CP: enhancer II and core promotor, ε: pregenome RNA encapsidation signal epsilon, SP I: surface promotor I, SP II: surface promotor II).
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Figure 2: Mutations identified in the HBV genomes from mothers and infants are illustrated. (C)The horizontal line represents the HBV nucleotide sequence of the reference genome (11). (A) The four open reading frames (ORF) are depicted in open bars. Lines within these bars represent mutations resulting in amino acid changes in the infant with fulminant disease. (B) Black bars in the middle indicate enhancer and promotor regions (GRE: Glucocorticoid response element, ENH I-XP: enhancer I and X promotor, ENH II-CP: enhancer II and core promotor, ε: pregenome RNA encapsidation signal epsilon, SP I: surface promotor I, SP II: surface promotor II).

Mentions: 27, 6, 43, 22 and 33 nucleotide exchanges were identified between the HBV isolates from mothers and infants. The mutations were distributed over the entire HBV genome and a few hot spots (Figure 2). Many mutations were rare or unique compared with the other genomes investigated. A specific mutation that occurred "de novo" in the HBV genomes of all 5 infants could not be identified. Several base pair exchanges occurred in at least 2 of the 5 infant HBV genomes investigated (nucleotides 144, 930, 1764, 1940, 2174, 2452, 2797, 3072, 3102). However, 4 mutations (nucleotides 1762, 3067 and 1896, 1899) were overrepresented (60–100%) in the cases of fulminant hepatitis compared to the chronic carriers (Figure 1).


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)

Mutations identified in the HBV genomes from mothers and infants are illustrated. (C)The horizontal line represents the HBV nucleotide sequence of the reference genome (11). (A) The four open reading frames (ORF) are depicted in open bars. Lines within these bars represent mutations resulting in amino acid changes in the infant with fulminant disease. (B) Black bars in the middle indicate enhancer and promotor regions (GRE: Glucocorticoid response element, ENH I-XP: enhancer I and X promotor, ENH II-CP: enhancer II and core promotor, ε: pregenome RNA encapsidation signal epsilon, SP I: surface promotor I, SP II: surface promotor II).
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Related In: Results  -  Collection

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

Figure 2: Mutations identified in the HBV genomes from mothers and infants are illustrated. (C)The horizontal line represents the HBV nucleotide sequence of the reference genome (11). (A) The four open reading frames (ORF) are depicted in open bars. Lines within these bars represent mutations resulting in amino acid changes in the infant with fulminant disease. (B) Black bars in the middle indicate enhancer and promotor regions (GRE: Glucocorticoid response element, ENH I-XP: enhancer I and X promotor, ENH II-CP: enhancer II and core promotor, ε: pregenome RNA encapsidation signal epsilon, SP I: surface promotor I, SP II: surface promotor II).
Mentions: 27, 6, 43, 22 and 33 nucleotide exchanges were identified between the HBV isolates from mothers and infants. The mutations were distributed over the entire HBV genome and a few hot spots (Figure 2). Many mutations were rare or unique compared with the other genomes investigated. A specific mutation that occurred "de novo" in the HBV genomes of all 5 infants could not be identified. Several base pair exchanges occurred in at least 2 of the 5 infant HBV genomes investigated (nucleotides 144, 930, 1764, 1940, 2174, 2452, 2797, 3072, 3102). However, 4 mutations (nucleotides 1762, 3067 and 1896, 1899) were overrepresented (60–100%) in the cases of fulminant hepatitis compared to the chronic carriers (Figure 1).

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