title: Evolutionary analysis of HBV "S" antigen genetic diversity in Iranian blood donors: a nationwide study.
abstract: The genetic diversity of the HBV S gene has a significant impact on the prophylaxis and treatment of hepatitis B infection. The effect of selective pressure on this genetic alteration has not yet been studied in Iranian blood donors. To explore HBV evolution and to analyze the effects and patterns of hepatitis B surface antigen (HBsAg) mutations on blood screening assays, 358 Iranian blood donors diagnosed as asymptomatic HBV carriers were enrolled in this nationwide study. Large S and partial S genes were amplified and sequenced. HBV (sub) genotypes and synonymous and nonsynonymous mutations were investigated. The impact of naturally occurring mutations on HBsAg ELISA results was explored. Phylogenetic analyses revealed that isolated strains were of genotype D. The dominant subgenotype/subtype was D1/ayw2. Deletions and naturally occurring stop codons in the pre-S1 and major hydrophilic region (MHR) were identified. In total, 32.8% of the studied strains harbored 195 single or multiple mutations in the MHR, the majority of which were located at the first loop of the "a determinant" domain. The ayw2 subtype showed a significant effect on the ELISA signal/cut-off value and carried fewer mutations in the MHR. Nonsynonymous/synonymous substitution value indicated that negative selection was the dominant evolutionary force in the HBV S gene. This nationwide study revealed that mutation frequency of HBsAg among Iranian blood donors was much higher than previous reports from the different local regions. These findings regarding the significant differences in reactivity of ELISA among different subtypes of HBV and its correlation with the number of mutations at the MHR will be valuable to public health authorities.
authors.affiliation: Department of Microbiology and Immunology, Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium; Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.
authors.forename: Mahmoud Reza
authors.initials: MR
authors.lastname: Pourkarim
authors.forename: Zohre
authors.initials: Z
authors.lastname: Sharifi
authors.forename: Ali
authors.initials: A
authors.lastname: Soleimani
authors.forename: Samad
authors.initials: S
authors.lastname: Amini-Bavil-Olyaee
authors.forename: Ahmed
authors.initials: A
authors.lastname: Elsadek Fakhr
authors.forename: Steven
authors.initials: S
authors.lastname: Sijmons
authors.forename: Jurgen
authors.initials: J
authors.lastname: Vercauteren
authors.forename: Gharib
authors.initials: G
authors.lastname: Karimi
authors.forename: Philippe
authors.initials: P
authors.lastname: Lemey
authors.forename: Piet
authors.initials: P
authors.lastname: Maes
authors.forename: Seyed Moayed
authors.initials: SM
authors.lastname: Alavian
authors.forename: Marc
authors.initials: M
authors.lastname: Van Ranst
mesh_terms: D000293:Adolescent; D000328:Adult; D001782:Blood Donors; D002353:Carrier State / Q000821:virology; D016000:Cluster Analysis; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D004797:Enzyme-Linked Immunosorbent Assay; D019143:Evolution, Molecular; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006509:Hepatitis B / Q000821:virology*; D006514:Hepatitis B Surface Antigens / Q000032:analysis / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D007492:Iran; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D059645:Mutation Rate; D020125:Mutation, Missense; D010802:Phylogeny; D017354:Point Mutation; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens
keywords: HBsAg; Iran; blood donors; evolution; hepatitis B virus; mutation