Analysis of S gene (HBs Ag) mutation in chronic hepatitis B patients and determination of their acquired immune escape pattern

Document Type : Research Paper


1 MS, Biotechnology, Islamic Azad University, Science and Research Branch, Tehran, Iran.

2 Associated professor, Molecular genetics, Razi Vaccine and Serum Research Institute, Agricultural Research Education and Extension Organization, Karaj, Iran.

3 MS, Biotechnology, Razi Vaccine and Serum Research Institute, Agricultural Research Education and Extension Organization, Karaj, Iran


Background: Mutant strains resistant to nucleoside/nucleotide analogs of hepatitis B virus (HBV) emerge due to the prolonged usage and single nucleotide polymorphism (SNP) incidence and escape mutations. The current study aimed to detect the selective pressures and the immune-associated escape mutation in HBsAg (S) gene in chronically HBV-infected patients.
Materials and Methods: In this cross-sectional study in 2013, fifty patients with chronic hepatitis B in Karaj were divided into treated and untreated groups. The number of virus DNA copies was quantified by real-time PCR and S gene was sequenced. The effect of each SNP on S protein stability was predicted with 1-mutant and DDG free energy estimation.
Results: The lowest and the highest viral load in the serum samples were estimated 1.1 × 101/ml and 4.3 × 108/ml copies, respectively. The highest number of mutations leading to amino acid substitution includes Q101R, T115N, S143L, and Q129P was determined in one person who used drug was identified. In one patient without treatment, the M133T and L175S mutations were observed. The Q129P, S174N, and Y134C were also seen in others with a history of treatment. Of the 8 amino acid changes, L175S with DDG equal to 1.87 Kcal/mol had the greatest reduction effect on S protein stability.
Conclusion: According to these data, there is a relationship between the SNP of the virus S gene and the emergence of escape mutations. Findings of studies of escape mutations in human populations can influence the improvement of treatment and immunization against chronic hepatitis B infection.


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