Mutation Hot Spots in Hepatitis B Surface Antigen in Chronic Carriers from Khoozestan Province, Southern of Iran

• Main Authors: Fatemeh Ramezani, Mehdi Norouzi, Gholam Reza Sarizade, Vahdat Poortahmasebi, Ebrahim Kalantar, Lars Magnius, Helen Norder, Esteban Domingo, Seyed Mohammad Jazayeri
• Format: Article
• Language: English
• Published: Tehran University of Medical Sciences 2013-09-01
• Series: Iranian Journal of Allergy, Asthma and Immunology
• Subjects: Chronic HBV; HBV escape mutations; HBV immune epitope; HBsAg mutation.
• Online Access: https://ijaai.tums.ac.ir/index.php/ijaai/article/view/503

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.