Author/Authors :
Ramezani Rad، Fatemeh نويسنده Master of Horticulture, Rasht Branch, Islamic Azad University, Rasht, Iran , , Norouzi، Mehdi نويسنده Hepatitis B Molecular Laboratory, Department of Virology-School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran , , Sarizade، Gholam Reza نويسنده Khoozestan Province Blood Trasfusion, Ahvaz, Iran Sarizade, Gholam Reza , Poortahmasebi، Vahdat نويسنده Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran , , Kalantar، Ebrahim نويسنده School of Allied Medical Sciences, Iran Medical University, Tehran , , Magnius، Lars نويسنده Virological Department, Swedish Institute for Infectious Disease Control, Solna, Sweden Magnius, Lars , Norder، Helen نويسنده Virological Department, Swedish Institute for Infectious Disease Control, Solna, Sweden Norder, Helen , Domingo، Esteban نويسنده Centro de Biolog?a Molecular, Severo Ochoa, (CSIC-UAM), Universidad Aut?noma de Madrid, Cantoblanco, Madrid, Spain Domingo, Esteban , Jazayeri، Seyed Mohammad نويسنده Hepatitis B Molecular Laboratory-Department of Virology-School of Public Health-Tehran University of Medical Sciences, Tehran ,
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 muta-tions 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.
