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Hepatitis B Virus Surface Protein Mutations Clustered Mainly in Ctl Immune Epitopes in Chronic Carriers: Results of an Iranian Nationwide Study Publisher Pubmed



Khedive A1 ; Norouzi M1 ; Ramezani F1 ; Karimzadeh H1 ; Alavian SM2 ; Malekzadeh R3 ; Montazeri G3 ; Nejatizadeh A4 ; Ziaee M5 ; Abedi F6 ; Ataei B7 ; Yaran M7 ; Sayad B8 ; Somi MH9 Show All Authors
Authors
  1. Khedive A1
  2. Norouzi M1
  3. Ramezani F1
  4. Karimzadeh H1
  5. Alavian SM2
  6. Malekzadeh R3
  7. Montazeri G3
  8. Nejatizadeh A4
  9. Ziaee M5
  10. Abedi F6
  11. Ataei B7
  12. Yaran M7
  13. Sayad B8
  14. Somi MH9
  15. Sarizadeh G10
  16. Saneimoghaddam I11
  17. Mansourghanaei F12
  18. Rafatpanah H13
  19. Pourhosseingholi MA14
  20. Keyvani H15
  21. Kalantari E16
  22. Saberifiroozi M17
  23. Judaki MA1
  24. Ghamari S1
  25. Daram M1
  26. Mahabadi M1
  27. Fazeli Z1
  28. Goodarzi Z1
  29. Poortahmasebi V1
  30. Jazayeri SM1
Show Affiliations
Authors Affiliations
  1. 1. Department of Virology, School of Public Health, Tehran University of Medical Sciences, Zip Code: 14155-6446, Tehran, P.O. Box: 15155-6446, Iran
  2. 2. Middle East Liver Diseases Center (MELD Centers), Tehran, Iran
  3. 3. Digestive Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Research Center for Molecular Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
  5. 5. Department of Internal Medicine, Vali-e-Asr Hospital, Birjand University of Medical Sciences, Birjand, Iran
  6. 6. Department of Infectious Disease, Mashhad University of Medical Sciences, Mashhad, Iran
  7. 7. Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
  8. 8. Kermanshah Liver Diseases and Hepatitis Research Center, Kermanshah, Iran
  9. 9. Liver and Gastrointestinal Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  10. 10. Educational Region of Khozestan Blood Transfusion Organization, Ahvaz, Iran
  11. 11. Department of Gastroenterology, Zahedan University of Medical Sciences, Zahedan, Iran
  12. 12. Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
  13. 13. Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
  14. 14. Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  15. 15. Department of Virology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  16. 16. Gholhack Medical Laboratory, Tehran, Iran
  17. 17. Digestive Disease Research Center, Gastroenterohepatology Research Center, Tehran and Shiraz University of Medical Sciences, Tehran and Shiraz, Iran

Source: Journal of Viral Hepatitis Published:2013


Abstract

Mutations within the coding region of hepatitis B surface antigen (HBsAg) have been found naturally in chronic carriers. To characterize the mutations of HBsAg from Iranian chronic carriers who were vaccine and/or medication naive. The surface genes from 360 patients were amplified and directly sequenced. The distribution of amino acid substitutions was classified according to different immune epitopes of the surface protein. All isolates belonged to genotype D. 222 (61.6%) of 360 patients contained at least one amino acid substitution. 404 (74.5%) of 542 amino acid changes occurred in different immune epitopes of HBsAg, of which 112 (27.7%) in 32 residues of B-cell epitopes (62 in the 'a' determinant); 111 (27.4%) in 32 residues of T helper; and 197 (48.7%) in 32 residues inside cytotoxic T lymphocyte (CTL) epitopes. One Th (186-197) and two CTL (28-51 and 206-215) epitopes were found to be hotspot motifs for the occurrence of 213 (52.7%) substitutions. 20 stop codons were identified in different epitopes. There was a significant association between amino acid substitutions and anti-HBe seropositivity; however, the correlation between such changes with viral load and ALT levels was not significant. In chronic hepatitis B virus(HBV) carriers, positive selection in particular outside the 'a' determinant appeared to exert influence on the surface proteins. These changes could be immune escape mutations naturally occurring due to the host immune surveillance especially at the T-cell level. © 2013 John Wiley & Sons Ltd.
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