title: Mutation hot spots in hepatitis B surface antigen in chronic carriers from Khoozestan province, southern of Iran.
abstract: Mutations in the human hepatitis B virus (HBV) genome contribute to its escape from host immune surveillance and result in persistent infections. The aim of this study was to characterize the molecular variations of the surface gene and protein in chronically-infected patients from the southern part of Iran. The surface genes from 12 HBV chronic carriers were amplified, sequenced and subsequently aligned using international and national Iranian database. All strains belonged to genotype D, subgenotype D1 and subtype ayw2. Of all 30 mutations occurred at 22 nucleotide positions, 18 (60%) were missense (amino acid altering) and 12 (40%) were silent (no amino acid changing). The mean mutation frequency (missense to silent nucleotide ratio), was 1.5, indicating application of a high positive selection pressure on the surface proteins. At the amino acid level, of 17 substitutions, 15 (88%) occurred in different immune epitopes within surface protein, of which 7 (46.6%) in B cell epitopes in 5 residues; 7 (46.6%) in T helper epitopes in 6 positions; 1 (7%) in inside CTL epitopes in 1 residue. We therefore conclude that the distribution of 93.2% of amino acid mutations inside B and T helper immune epitopes as well as the ratio between silent and missense nucleotide mutations showed a positive, focused immune selection pressure on the surface protein, which led to the evolution and emergence of escape mutants in these patients.
authors.affiliation: Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. fatemehramezani23@yahoo.com.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Ramezani
authors.forename: Mehdi
authors.initials: M
authors.lastname: Norouzi
authors.forename: Gholam Reza
authors.initials: GR
authors.lastname: Sarizade
authors.forename: Vahdat
authors.initials: V
authors.lastname: Poortahmasebi
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Kalantar
authors.forename: Lars
authors.initials: L
authors.lastname: Magnius
authors.forename: Helen
authors.initials: H
authors.lastname: Norder
authors.forename: Esteban
authors.initials: E
authors.lastname: Domingo
authors.forename: Seyed Mohammad
authors.initials: SM
authors.lastname: Jazayeri
mesh_terms: D019943:Amino Acid Substitution; D002353:Carrier State / Q000276:immunology*; D003430:Cross-Sectional Studies; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006801:Humans; D007492:Iran; D009154:Mutation; D010802:Phylogeny
chemical_list: D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D006514:Hepatitis B Surface Antigens