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. 2019 Jul 1;11(1):e2019046.
doi: 10.4084/MJHID.2019.046. eCollection 2019.

Nucleotide Substitutions in Hepatitis B Viruses Derived from Chronic HBV Patients

Narjes Shokatpour  1 , Maryam Vaezjalali  2   3 , Graham R Foster  4 , Shahnaz Sali  2
Affiliations

Nucleotide Substitutions in Hepatitis B Viruses Derived from Chronic HBV Patients

Narjes Shokatpour et al. Mediterr J Hematol Infect Dis. .

Abstract

Background: Mutations in the S gene (HBsAg), pre-core (PC), and basic core promoter (BCP) of the hepatitis B virus (HBV) infection are correlated with disease progression. This study assessed the frequency of mutations in the S gene, PC, and BCP regions in chronic hepatitis B (CHB) patients.

Methods: 104 formerly known CHB patients who visited Tehran Hepatitis centers, were included. The viral load of samples was determined based on the TaqMan method. Regions of the S gene, PC and BCP were amplified by the nested PCR. Positive PCR products were sequenced and analyzed.

Results: 33 successfully sequenced S gene region revealed all the derived strains were genotype D, with the majority (90.9%) belonging to the ayw2 subtype, and the rest (9.1%) to the ayw1 subtype. The prevalence of mutations was found to be 51.0% and 18.0% in the HBsAg and the Major Hydrophilic Region, respectively. 70.0% of amino acid changes within HBsAg occurred in different immune epitopes, of which 27.0% and 72.0% were located in B cell and Th epitopes, respectively. 26 successfully sequenced PC and BCP regions showed at least one mutation in 84.6% of the HBV strains. The PC and BCP mutations were G1896A (61.0%), G1899A (23.0%), A1762T/G1764A (23.0%) and G1764T/C1766G (26.0%). None of the strains with A1762T/G1764A mutation carried the G1764T/C1766G mutant.

Conclusions: Our results showed common mutations within HBsAg, occurring in immune epitopes, a high rate of G1896A mutations in the PC region, and a negative correlation between the emergence of A1762T/G1764A mutation and the G1764T/C1766G mutant in the BCP region.

Keywords: Chronic hepatitis B; Hepatitis B e antigen; Hepatitis B surface antigen; Hepatitis B virus; Mutation.

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Conflict of interest statement

Competing interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1
Amino acid mutations within B cell, T helper (Th) and CTL epitopes of HBs proteins. Amino acids are designated by single letter code and numbered from the beginning of HBsAg.
Figure 1
Figure 1
Amino acid mutations within B cell, T helper (Th) and CTL epitopes of HBs proteins. Amino acids are designated by single letter code and numbered from the beginning of HBsAg.
Figure 2
Figure 2
UPGMA phylogenetic tree of surface genes sequences from 33 HBV strains. The tree rooted with HBV Woolly Monkey (AY226578) sequence. Genetic distances were estimated using the Kimura 2-parameter matrix. Clustering of sequences was supported by 1000 resamplings of the data sets.
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References

    1. Agarwal A, Sen S, Banerjee D, Srivastava R, Praharaj A. Distribution of hepatitis B virus genotype and cancer predicting precore and basal core promoter mutations. Medical Journal Armed Forces India. 2015;71(3):225–232. - PMC - PubMed
    1. Wang X-L, Ren J-P, Wang X-Q, Wang X-H, Yang S-F, Xiong Y. Mutations in pre-core and basic core promoter regions of hepatitis B virus in chronic hepatitis B patients. World Journal of Gastroenterology. 2016;22(11):3268. doi: 10.3748/wjg.v22.i11.3268. - DOI - PMC - PubMed
    1. Assih M, Ouattara AK, Diarra B, Yonli AT, Compaore TR, Obiri-Yeboah D, Djigma FW, Karou S, Simpore JJ. Wjoh: Genetic diversity of hepatitis viruses in West-African countries from 1996 to 2018. World J Hepatol. 2018 Nov 27;10(11):807–821. doi: 10.4254/wjh.v10.i11.807. - DOI - PMC - PubMed
    1. Echevarría JM, Avellón A. Hepatitis B virus genetic diversity. Journal of Medical Virology. 2006;78(S1):S36–S42. doi: 10.1002/jmv.20605. - DOI - PubMed
    1. Pujol FH, Navas M-C, Hainaut P, Chemin I. Worldwide genetic diversity of HBV genotypes and risk of hepatocellular carcinoma. Cancer Letters. 2009;286(1):80–88. doi: 10.1016/j.canlet.2009.07.013. - DOI - PubMed