High level of genetic heterogeneity in S and P genes of genotype D hepatitis B virus.

C. de Maddalena,C. Giambelli,E. Tanzi,D. Colzani,M. Schiavini,L. Milazzo,Flavia Bernini,Erika Ebranati,A. Cargnel,R. Bruno,M. Galli,G. Zehender

Published 2007 in Virology

ABSTRACT

The genetic heterogeneity of hepatitis B virus (HBV) genotypes and subgenotypes was investigated by directly sequencing amplified PreS, S and P genes of HBV isolates obtained from the plasma of 99 subjects with chronic HBV infection. Genotype D showed the greatest intragenotypic and intrasubgenotypic divergence: in particular, the a determinant was mutated in 58.2% of the genotype D patients, two of whom showed prototypic vaccine-induced escape mutants at codon 145. Moreover, five sites under significant positive selection were found in the S protein of the D isolates: one in the a determinant and four in the highly hydrophobic C terminal. Our results suggest that careful surveillance of vaccine-induced escape mutants should be considered in populations with highly frequent genotype D infections, and raise questions concerning the possible relationship between the genetic heterogeneity, host immunity and pathogenicity of this HBV genotype.

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