High level of genetic heterogeneity in S and P genes of genotype D hepatitis B virus.
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.
De Maddalena
Chiara
C
Department of Clinical Sciences Luigi Sacco, Section of Infectious Diseases, University of Milan, Milan, Italy.
Giambelli
Camilla
C
Tanzi
Elisabetta
E
Colzani
Daniela
D
Schiavini
Monica
M
Milazzo
Laura
L
Bernini
Flavia
F
Ebranati
Erika
E
Cargnel
Antonietta
A
Bruno
Raffaele
R
Galli
Massimo
M
Zehender
Gianguglielmo
G
D000595:Amino Acid Sequence; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D018740:Genetic Heterogeneity; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000032:analysis* / Q000737:chemistry / Q000235:genetics*; D015611:Hepatitis B Virus, Duck / Q000145:classification / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010802:Phylogeny; D017422:Sequence Analysis, DNA
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens