title: Hepatitis B virus surface protein mutations clustered mainly in CTL immune epitopes in chronic carriers: results of an Iranian nationwide study.
abstract: Mutations within the coding region of hepatitis B surface antigen (HBsAg) have been found naturally in chronic carriers. To characterize the mutations of HBsAg from Iranian chronic carriers who were vaccine and/or medication naive. The surface genes from 360 patients were amplified and directly sequenced. The distribution of amino acid substitutions was classified according to different immune epitopes of the surface protein. All isolates belonged to genotype D. 222 (61.6%) of 360 patients contained at least one amino acid substitution. 404 (74.5%) of 542 amino acid changes occurred in different immune epitopes of HBsAg, of which 112 (27.7%) in 32 residues of B-cell epitopes (62 in the 'a' determinant); 111 (27.4%) in 32 residues of T helper; and 197 (48.7%) in 32 residues inside cytotoxic T lymphocyte (CTL) epitopes. One Th (186-197) and two CTL (28-51 and 206-215) epitopes were found to be hotspot motifs for the occurrence of 213 (52.7%) substitutions. 20 stop codons were identified in different epitopes. There was a significant association between amino acid substitutions and anti-HBe seropositivity; however, the correlation between such changes with viral load and ALT levels was not significant. In chronic hepatitis B virus(HBV) carriers, positive selection in particular outside the 'a' determinant appeared to exert influence on the surface proteins. These changes could be immune escape mutations naturally occurring due to the host immune surveillance especially at the T-cell level.
authors.affiliation: Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: A
authors.initials: A
authors.lastname: Khedive
authors.forename: M
authors.initials: M
authors.lastname: Norouzi
authors.forename: F
authors.initials: F
authors.lastname: Ramezani
authors.forename: H
authors.initials: H
authors.lastname: Karimzadeh
authors.forename: S M
authors.initials: SM
authors.lastname: Alavian
authors.forename: R
authors.initials: R
authors.lastname: Malekzadeh
authors.forename: G
authors.initials: G
authors.lastname: Montazeri
authors.forename: A
authors.initials: A
authors.lastname: Nejatizadeh
authors.forename: M
authors.initials: M
authors.lastname: Ziaee
authors.forename: F
authors.initials: F
authors.lastname: Abedi
authors.forename: B
authors.initials: B
authors.lastname: Ataei
authors.forename: M
authors.initials: M
authors.lastname: Yaran
authors.forename: B
authors.initials: B
authors.lastname: Sayad
authors.forename: M H
authors.initials: MH
authors.lastname: Somi
authors.forename: G
authors.initials: G
authors.lastname: Sarizadeh
authors.forename: I
authors.initials: I
authors.lastname: Sanei-Moghaddam
authors.forename: F
authors.initials: F
authors.lastname: Mansour-Ghanaei
authors.forename: H
authors.initials: H
authors.lastname: Rafatpanah
authors.forename: M A
authors.initials: MA
authors.lastname: Pourhosseingholi
authors.forename: H
authors.initials: H
authors.lastname: Keyvani
authors.forename: E
authors.initials: E
authors.lastname: Kalantari
authors.forename: M
authors.initials: M
authors.lastname: Saberifiroozi
authors.forename: M A
authors.initials: MA
authors.lastname: Judaki
authors.forename: S
authors.initials: S
authors.lastname: Ghamari
authors.forename: M
authors.initials: M
authors.lastname: Daram
authors.forename: M
authors.initials: M
authors.lastname: Mahabadi
authors.forename: Z
authors.initials: Z
authors.lastname: Fazeli
authors.forename: Z
authors.initials: Z
authors.lastname: Goodarzi
authors.forename: V
authors.initials: V
authors.lastname: Poortahmasebi
authors.forename: S M
authors.initials: SM
authors.lastname: Jazayeri
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D002353:Carrier State / Q000821:virology*; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000235:genetics* / Q000276:immunology; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000235:genetics* / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D057131:Immune Evasion; D007492:Iran; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D017422:Sequence Analysis, DNA; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D004279:DNA, Viral; D018984:Epitopes, T-Lymphocyte; D006514:Hepatitis B Surface Antigens