THE HEPATITIS-B VIRUS SEROCONVERSION TO ANTI-HBE IS FREQUENTLY ASSOCIATED WITH HBV GENOTYPE CHANGES AND SELECTION OF PRES2-DEFECTIVE PARTICLES IN CHRONICALLY INFECTED CHILDREN
Pr. Gerner et al., THE HEPATITIS-B VIRUS SEROCONVERSION TO ANTI-HBE IS FREQUENTLY ASSOCIATED WITH HBV GENOTYPE CHANGES AND SELECTION OF PRES2-DEFECTIVE PARTICLES IN CHRONICALLY INFECTED CHILDREN, Virology, 245(1), 1998, pp. 163-172
In order to investigate the generation and selection of hepatitis B vi
rus mutants and the influence of interferon on their evolution, a long
itudinal study including 22 patients was performed. The complete preS1
/S2 open reading frame was analyzed by direct sequencing from serum sa
mples obtained before and after seroconversion to anti-HBe in 11 child
ren without @-interferon treatment. Furthermore, in 11 cases with ther
apy additional samples obtained during interferon therapy were investi
gated. The comparison of each patient's preS sequences analyzed before
and during therapy did not show any nucleotide change, while in both
groups numerous silent and missense mutations were found immediately a
fter seroconversion. Surprisingly, in 7 cases the hepatitis B virus ch
anged genotype from A to D (subtype adw to ayw) after seroconversion.
Additional rearrangements were observed in 4 patients. In 3 cases the
selection of preS2 start codon mutants was detected after seroconversi
on and in 1 individual a 183-nucleotide deletion was found during and
after HBeAg positivity. In conclusion, the emergence of preS rearrange
ments and numerous base exchanges provide evidence for a strong select
ion process focused against the preS region. Moreover, the appearance
of genotype changes after anti-HBe seroconversion reveales a thus far
unrecognized event during the natural course of HBV infection in child
hood. (C) 1998 Academic Press.