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Mutations in the S gene region of hepatitis B virus genotype D in Golestan Province-Iran

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Abstract

Mutations of HBsAg especially within the “a” determinant could alter the antigenicity of the protein causing failure of HBsAg neutralization and escaping from the host’s immune system, resulting in active viral replication and liver disease. This project aimed to investigate mutation in the S gene region of HBV infected patients in Golestan Province-Iran. HBV-DNA extractions from plasma and PCR of 100 patients were performed. Direct sequencing and alignment of S gene were applied using reference sequence from Gene Bank database. All isolates were belonged to genotype D, subgenotype D1, subtype ayw2. Overall 92 point mutations occurred. Of them, 40 (43.47%) were missense and 52 (56.52%) were silent. Mutations were detected in 95 cases (95%). Five of 40 mutations (12.5%) occurred in “a” determinant and 13 (32.5%), 17 (42.5%), and 2 (5%) were seen in antigenic epitope regions of B cell, CD4 + and CTL, respectively. Frame shift mutations were seen in 22 cases (22%). 14% of mutations occurred at Major Hydrophilic Region(MHR) area which P120T/S and R122K/T substitutions were the most frequent ones (4%). Mutation in G145R of the S gene was observed in one case. A large number of MHR mutants are in association with failure of HBsAg detection, vaccine, and immunotherapy escape. This study showed “a” determinant S gene mutations in HBV infected people with HBsAg positivity in Golestan Province-Iran. The rate of mutation in our study was 95%. Collectively, the results of this project exhibited that most of mutations were clustered in CD4 + antigenic epitopes.

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References

  1. S.M. Akbar, S. Furukawa, N. Horiike, M. Onji, Vaccine therapy for hepatitis b virus. Curr. Drug Target Infect. Disord. 4(2), 93–101 (2004)

    Article  CAS  Google Scholar 

  2. H.-Y. Lu et al., Mutation in surface and polymerase gene of chronic hepatitis B patients with coexisting HBsAg and anti-HBs. World J. Gastroenterol. 12(26), 4219–4223 (2006)

    PubMed  CAS  Google Scholar 

  3. H. Norder et al., Genetic diversity of hepatitis B virus strains derived worldwide: genotypes, subgenotypes, and HBsAg subtypes. Intervirology 47, 289–309 (2004)

    Article  PubMed  Google Scholar 

  4. K. Yamamoto et al., Naturally occurring escape mutants of hepatitis B virus with various mutations in the S gene in carriers seropositive for antibody to hepatitis B surface antigen. J. Virol. 68(4), 2671–2676 (1994)

    PubMed  CAS  Google Scholar 

  5. P.F. Coleman, Detecting hepatitis B surface antigen mutation. Emerg. Infect. Dis. 12(2), 198–202 (2006)

    Article  PubMed  CAS  Google Scholar 

  6. M. Ozaslan, E. Ozaslan, A. Barsgan, M. Koruk, Mutations in the S gene region of hepatitis B virus genotype D in Turkish patients. J. Genetics 86(3), 195–201 (2007)

    Article  CAS  Google Scholar 

  7. V. Velu, Sh. Saravanan, S. Nandakumar, E. Dhevahi, E.M. Shankar et al., Transmission of “a” determinant variants of hepatitis B virus in immunized babies born to HBsAg carriers mothers. Jpn. J. Infect. Dis. 61, 73–76 (2008)

    PubMed  CAS  Google Scholar 

  8. M. Norouzi et al., Hepatitis B virus surface antigen variants clustered within immune epitopes in chronic hepatitis B carriers from Hormozgan Province, south of Iran. Iran. J. Basic Med. Sci. 13(4), 213–224 (2010)

    CAS  Google Scholar 

  9. J.-M. Pawlotsky, The concept of hepatitis B virus mutant escape. J. Clin. Virol. 34(Suppl.1), 125–129 (2005)

    Article  Google Scholar 

  10. W.E. Delaney, H. Yang, C.E. Westland, K. Das, E. Arnold et al., The hepatitis B virus polymerase mutation rtV173L is selected during lamivudine therapy and enhances viral replication in vitro. J. Virol. 77(21), 11833–11841 (2003)

    Article  PubMed  CAS  Google Scholar 

  11. S.M. Alavian, F. Fallahian, K. Bagheri-Lankarani, The changing epidemiology of viral hepatitis B in Iran. J. Gastrointestin. Liver Dis. 16(4), 403–406 (2007)

    PubMed  Google Scholar 

  12. Gh. Roshandel, Sh. Semnani, A. Keshtkar, H. Joshaghani, A. Moradi et al., Seroprevalence of hepatitis B virus and its co-infection with hepatitis D and hepatitis C in Iranian adult population. Indian J. Med. Sci. 61(5), 263–268 (2007)

    Article  Google Scholar 

  13. A. Moradi, Response to the hepatitis B virus vaccine in Iranian infants. Hepat. Mon. 3, 229–231 (2009)

    Google Scholar 

  14. H. Okamoto, F. Tsuda, H. Sakugawa, R.I. Sastrosoewignjo, M. Imai et al., Typing hepatitis B virus by homology in nucleotide sequence: comparison of surface antigen subtypes. J. Gen. Virol. 69(PT 10), 2575–2583 (1988)

    Article  PubMed  CAS  Google Scholar 

  15. A. Moradi et al., Hepatitis B virus genotyping in Iran. Indian J. Med. Sci. 62(5), 204–205 (2008)

    Article  PubMed  Google Scholar 

  16. M. Daram, R. Malekzadeh, Gh. Montazeri, S.M. Alavian, Sh. Mirmomen, Identification of HBV surface Ag variants in patients with hepatitis before and after immunization. Govaresh 12(4), 229–234 (2008)

    Google Scholar 

  17. R. Hamkar et al., Surface gene mutations of hepatitis B virus among high-risk patients with occult hepatitis B virus infection. Diagn. Microbiol. Infect. Dis. 66(3), 289–291 (2010)

    Article  Google Scholar 

  18. H.-B. Chen et al., A novel hepatitis B virus mutant with A-to-G at nt551 in the surface antigen gene. World J. Gastroenterol. 9(2), 304–308 (2003)

    PubMed  CAS  Google Scholar 

  19. I. Lazarevic et al., Prevalence of hepatitis B virus MHR mutations and their correlation with genotypes and antiviral therapy in chronically infected patients in Serbia. J. Med. Virol. 82(7), 1160–1167 (2010)

    Article  PubMed  CAS  Google Scholar 

  20. Y.L.F.G. Pineiro et al., Hepatitis B virus genetic diversity in Argentina: dissimilar genotype distribution in two different geographical regions; description of hepatitis B surface antigen variants. J. Clin. Virol. 42, 381–388 (2008)

    Article  Google Scholar 

  21. N. Khan et al., Modulation of hepatitis B virus secretion by naturally occurring mutations in the S gene. J. Virol. 78(7), 3262–3270 (2004)

    Article  PubMed  CAS  Google Scholar 

  22. C. De Maddalena et al., High level of genetic heterogeneity in S and P genes of genotype D hepatitis B virus. Virology 365, 113–124 (2007)

    Article  PubMed  Google Scholar 

  23. J. Sheldon, V. Soriano, Hepatitis B virus escape mutants induced by antiviral therapy. J. Antimicrob. Chemother. 61, 766–768 (2008)

    Article  PubMed  CAS  Google Scholar 

  24. X. Huang, D. Lu et al., Hepatitis B virus (HBV) vaccine-induced escape mutants of HBV S gene among children from Qidong of China. Virus Res. 99, 63–68 (2004)

    Article  PubMed  CAS  Google Scholar 

  25. A. Theamboonlers, V. Chongsrisawat, P. Jantaradsamee, Y. Poovorawan, Variants within the a determinant of HBs gene in children and adolescents with and without hepatitis B vaccination as parts of Thailand’s expanded program on immunization. Tohoko J. Exp. Med. 193, 197–205 (2001)

    Article  CAS  Google Scholar 

  26. A. Avellon, J.M. Echevarria, Frequency of hepatitis B virus “a” determinant variants in unselected Spanish chronic carriers. J. Med. Virol. 78, 24–36 (2006)

    Article  PubMed  Google Scholar 

  27. B. Kitab et al., Hepatitis B genotypes/subgenotypes and MHR variants among Moroccan chronic carriers. J. Infect. 63(1), 66–75 (2011)

    Article  PubMed  Google Scholar 

  28. C.J. Oon, G.K. Lim, Z. Ye et al., Molecular epidemiology of hepatitis B virus vaccine variants in Singapore. Vaccine 13, 692–702 (1995)

    Article  Google Scholar 

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Correspondence to Alijan Tabarraei.

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Moradi, A., Zhand, S., Ghaemi, A. et al. Mutations in the S gene region of hepatitis B virus genotype D in Golestan Province-Iran. Virus Genes 44, 382–387 (2012). https://doi.org/10.1007/s11262-012-0715-z

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  • DOI: https://doi.org/10.1007/s11262-012-0715-z

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