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.

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, F. Bernini, E. Ebranati, A. Cargnel, R. Bruno, M. Galli, G. Zehender. - In: VIROLOGY. - ISSN 0042-6822. - 365:1(2007 Aug 15), pp. 113-124. [10.1016/j.virol.2007.03.015]

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

C. De Maddalena
Primo
;
C. Giambelli
Secondo
;
E. Tanzi;D. Colzani;F. Bernini;E. Ebranati;M. Galli
Penultimo
;
G. Zehender
Ultimo
2007

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.
Genetic heterogeneity; Genetic variability; Genotypes; Hepatitis B virus; Molecular evolution; Natural selection; Pathogenesis
Settore MED/42 - Igiene Generale e Applicata
Settore MED/17 - Malattie Infettive
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/37795
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