Hepatitis B virus surface antigen (HBsAg) mutations are rare but clustered in immune epitopes in chronic carriers from Sistan-Balouchestan Province, Iran.

BACKGROUND Hepatitis B virus (HBV) gene and protein variations have frequently been observed in chronic patients. The aims of this study were to determine the genotypes as well as the patterns of HBsAg variations in chronically-infected patients from the south-eastern part of Iran. METHODS Twenty- one chronic inactive HBV carriers from Sistan-Balouchestan Province (an area with a low prevalence of HBV complications such as cirrhosis and hepatocellular carcinoma [HCC]) were enrolled. The surface genes were amplified, sequenced, and subsequently aligned using international and national Iranian database. RESULTS All strains belonged to genotype D, subgenotype D1, and subtype ayw2. Of all 39 mutations occurred at 31 nucleotide positions, 15 (38.5%) were missense (amino acid altering) and 24 (61.5%) were silent (no amino acid changing). At the amino acid level, 15 substitutions occurred; 10 (66.67%) were distributed in different immune epitopes, five of which (33.33%) were in B cell epitopes; four (36.27%) were distributed in T helper epitopes, and one (6.67%) occurred inside CTL epitopes. CONCLUSION A narrowly-focused immune pressure has been on the surface proteins, especially at the B cell level, led to the emergence of escape mutants in these patients that might be related to the pathogenicity of HBV chronic infection. Also, due to the negative selection imposed on HBV genome and the uniqueness of genotype D in this ethnic group, complications (cirrhosis and HCC) are lower than other published studies.