Complete hepatitis B virus genome analysis in HBsAg positive mothers and their infants with fulminant hepatitis B.
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.
Friedt
Michael
M
Department of Pediatrics, University of Zurich, Steinwiesstr. 75, CH-8032 Zurich, Switzerland. mfriedt@web.de
Gerner
Patrick
P
Wintermeyer
Philip
P
Wirth
Stefan
S
D000328:Adult; D000595:Amino Acid Sequence; D020137:Base Pair Mismatch / Q000235:genetics; D001483:Base Sequence; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D014644:Genetic Variation; D006509:Hepatitis B / Q000635:transmission* / Q000821:virology*; D006515:Hepatitis B virus / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D011401:Promoter Regions, Genetic / Q000235:genetics
D004279:DNA, Viral