Mutation hot spots in hepatitis B surface antigen in chronic carriers from Khoozestan Province, Southern of Iran

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...

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Detalles Bibliográficos
Autores: Ramezani, Fatemeh, Norouzi, Mehdi, Sarizade, Gholam R., Poortahmasebi, Vahdat, Kalantar, Ebrahim, Magnius, Lars, Norder, Heléne, Domingo, Esteban, Jazayeri, Seyed Mohammad
Tipo de recurso: artículo
Fecha de publicación:2013
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/98069
Acceso en línea:http://hdl.handle.net/10261/98069
Access Level:acceso abierto
Palabra clave:Chronic HBV
HBV escape mutations
HBsAg mutation
HBV immune epitope
Descripción
Sumario: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. Copyright© Autumn 2013, Iran J Allergy Asthma Immunol. All rights reserved.