Skip to main content

Advertisement

SpringerLink
Log in

Molecular characterization of hepatitis B virus X gene in HIV-positive South Africans

  • Published:
Virus Genes Aims and scope Submit manuscript

Abstract

Hepatitis B virus (HBV) infection is a major public health problem worldwide and the major cause of hepatocellular carcinoma (HCC) in South Africa. The role of HBV in HCC is not well understood, although the HBV X gene has been implicated as a critical factor. Data on the HBV X gene in HIV-positive South Africans are limited; thus, we investigated X gene variability in 24 HIV-infected treatment-naïve patients at Dr George Mukhari Academic Hospital. Quantitative and qualitative HBV DNA tests were conducted using real-time and in-house polymerase chain reaction (PCR) assays, respectively, targeting the complete HBV X gene. In-house PCR-positive samples were cloned using the P-Gem T-easy vector System II and sequenced. By phylogenetic analysis, X gene sequences were classified as subgenotype A1 (n = 15), A2 (n = 4), and D1 (n = 4), and one dual infection with subgenotypes as A1 and C. The basal core promoter mutations T1753C, A1762T, and G1764A were identified in the majority of sequences. Genotype D sequences had a 6-nucleotide insertion. In conclusion, subgenotype A1 was predominant, and a rare dual infection of HBV genotype A and C was detected. The 6-nucleotide insertion could represent a unique variant in the region and highlights the need for functional studies of HBV X gene variants, particularly from resource-limited settings.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. World Health Organization. Hepatitis B fact sheet

  2. D. Lavanchy, J. Clin. Virol. 34, S1–S3 (2005)

    Article  PubMed  Google Scholar 

  3. M. Lemoine, M. Thursz, J. Hepatol. 66, 645–654 (2017)

    Article  PubMed  Google Scholar 

  4. J.D. Yang, A. Gyedu, M.Y. Afihene, B.M. Duduyemi, E. Micah, T.P. Kingham, M. Nyirenda, A.A. Nkansah, S. Bandoh, M.J. Duguru, E.N. Okeke, M.J. Kouakou-Lohoues, A. Abdo, Y.A. Awuku, A.O. Ajayi, A.E. Omonisi, P. Ocama, A.O. Malu, S. Mustapha, U. Okonkwo, M. Kooffreh-Ada, J.D. Debes, C. Onyekwere, F. Ekere, I. Rufina, Roberts LR, and the Africa Network for Gastrointestinal and Liver Diseases. Am. J. Gastroenterol. 110, 1629–1631 (2015)

    Article  CAS  PubMed  Google Scholar 

  5. G.D. Kirk, O.A. Lesi, M. Mendy, A.O. Akano, O. Sam, J.J. Goedert, P. Hainaut, A.J. Hall, H. Whittle, R. Montesano, Hepatology 39, 211–219 (2004)

    Article  PubMed  Google Scholar 

  6. A. Maldonado-Rodriguez, A.M. Cevallos, O. Rojas-Montes, K. Enriquez-Navarro, M.T. Alvarez-Muñoz, R. Lira, World J. Hepatol. 7, 253–260 (2015)

    Article  PubMed  PubMed Central  Google Scholar 

  7. G. Raimondo, J.P. Allain, M.R. Brunetto, M.A. Buendia, D.S. Chen, M. Colombo, A. Craxì, F. Donato, C. Ferrari, G.B. Gaeta, W.H. Gerlich, M. Levrero, S. Locarnini, T. Michalak, M.U. Mondelli, J.M. Pawlotsky, T. Pollicino, D. Prati, M. Puoti, D. Samuel, D. Shouval, A. Smedile, G. Squadrito, C. Trépo, E. Villa, H. Will, A.R. Zanetti, F. Zoulim, J. Hepatol. 49, 652–657 (2008)

    Article  PubMed  Google Scholar 

  8. J. Samal, M. Kandpal, P. Vivekanandan, Clin. Microbiol. Rev. 25, 142–163 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. M.C. Kew, R. Welschinger, R. Viana, J. Gastrenterol. Hepatol. 23, 1426–1430 (2008)

    Article  CAS  Google Scholar 

  10. M. Kew, Hepat. Mon. 12, e7876 (2012)

    PubMed  PubMed Central  Google Scholar 

  11. R.J. Burnett, G. François, M.C. Kew, G. Leroux-Roels, A. Meheus, A.A. Hoosen, M. Mphahlele, Liver Int. 25, 201–213 (2005)

    Article  CAS  PubMed  Google Scholar 

  12. C. Firnhaber, A. Reyneke, D. Schulze, B. Malope, M. Maskew, P. MacPhail, I. Sanne, A.D. Bisceglie, S. Afr. Med. J. 98, 541–544 (2008)

    PubMed  PubMed Central  Google Scholar 

  13. A. Lukhwareni, R.J. Burnett, S.G. Selabe, M.O. Mzileni, M. Mphahlele, J. Med. Virol. 81, 406–412 (2009)

    Article  CAS  PubMed  Google Scholar 

  14. M.J. Bouchard, R. Schneider, J. Virol. 78, 12725–12734 (2004)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. A.S. Lok, U. Akarca, S. Greene, Proc. Natl. Acad. Sci. USA 91, 4077–4081 (1994)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. C.M. Hunt, J.M. McGill, M.I. Allen, L. Condreay, Hepatology 31, 1037–1044 (2000)

    Article  CAS  PubMed  Google Scholar 

  17. S. Schaefer, J. Viral Hepat. 12, 111–124 (2005)

    Article  CAS  PubMed  Google Scholar 

  18. S. Tanwar, G. Dusheiko, Curr. Gastroenterol. Rep. 14, 37–46 (2012)

    Article  PubMed  Google Scholar 

  19. H. Okamoto, M. Imai, M. Kametani, T. Nakamura, M. Mayumi, Jpn. J. Exp. Med. 57, 231–236 (1987)

    CAS  PubMed  Google Scholar 

  20. J. Pawlotsky, J. Clin. Virol. 34, S125–S129 (2005)

    Article  CAS  PubMed  Google Scholar 

  21. J.A. Garson, P.R. Grant, U. Ayliffe, R.B. Ferns, R. Tedder, J. Virol. Methods 126, 207–213 (2005)

    Article  CAS  PubMed  Google Scholar 

  22. T.G. Bell, A. Kramvis, Viruses 7, 781–797 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. G.C. Kimbi, A. Kramvis, M. Kew, J. Gen. Virol. 85, 1211–1220 (2004)

    Article  CAS  PubMed  Google Scholar 

  24. A. Kramvis, M. Kew, Hepatol. Res. 37, S9–S19 (2007)

    Article  PubMed  Google Scholar 

  25. S.G. Selabe, E. Song, R.J. Burnett, M. Mphahlele, J. Med. Virol. 81, 996–1001 (2009)

    Article  CAS  PubMed  Google Scholar 

  26. A. Kramvis, Intervirology 57, 141–150 (2014)

    Article  PubMed  Google Scholar 

  27. E.A. Powell, M.P. Gededzha, M. Rentz, N.J. Rakgole, S.G. Selabe, T.A. Seleise, M.J. Mphahlele, J. Blackard, J. Med. Virol. 2015, 3 (2015)

    Google Scholar 

  28. C. Firnhaber, C.Y. Chen, D. Evans, M. Maskew, D. Schulz, A. Reyneke, A. Kramvis, Int. J. Infect. Dis. 16, e268–e272 (2012)

    Article  PubMed  Google Scholar 

  29. B.F. Chen, C.J. Liu, G.M. Jow, P.J. Chen, J.H. Kao, D. Chen, J. Gen. Virol. 87, 39–49 (2006)

    Article  CAS  PubMed  Google Scholar 

  30. N.L. Toan, H. le Song, P.G. Kremsner, D.N. Duy, V.Q. Binh, B. Koeberlein, S. Kaiser, R. Kandolf, J. Torresi, C. Bock, Hepatology 43, 1375–1384 (2006)

    Article  CAS  PubMed  Google Scholar 

  31. C.M. Martin, J.A. Welge, J. Blackard, J. Med. Virol. 83, 1142–1150 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. J.H. Kao, P.J. Chen, M.Y. Lai, D. Chen, Hepatology 34, 817–823 (2001)

    Article  CAS  PubMed  Google Scholar 

  33. K. Takahashi, Y. Akahane, K. Hino, Y. Ohta, S. Mishiro, Arch. Virol. 143, 2313–2326 (1998)

    Article  CAS  PubMed  Google Scholar 

  34. M. López-Cabrera, J. Letovsky, K.Q. Hu, A. Siddiqui, Proc. Natl. Acad. Sci. USA 87, 5069–5073 (1990)

    Article  PubMed  PubMed Central  Google Scholar 

  35. V.E. Buckwold, Z. Xu, M. Chen, T.S. Yen, J. Ou, J. Virol. 70, 5845–5851 (1996)

    CAS  PubMed  PubMed Central  Google Scholar 

  36. M. Baptista, A. Kramvis, M. Kew, Hepatology 29, 946–953 (1999)

    Article  CAS  PubMed  Google Scholar 

  37. Z. Abbas, R. Muzaffar, A. Siddiqui, S.A. Naqvi, S. Rizvi, BMC Gastroenterol. 6, 20 (2006)

    Article  PubMed  PubMed Central  Google Scholar 

  38. S. Parekh, F. Zoulim, S.H. Ahn, A. Tsai, J. Li, S. Kawai, N. Khan, C. Trépo, J. Wands, S. Tong, J. Virol. 77, 6601–6612 (2003)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. H.J. Kwun, K. Jang, Nucleic Acids Res. 32, 2202–2213 (2004)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. A. Utama, S. Purwantomo, M.D. Siburian, R. Dhenni, R.A. Gani, I. Hasan, A. Sanityoso, U.A. Miskad, F. Akil, I. Yusuf, W.A. Achwan, S. Soemohardjo, S.A. Lelosutan, R. Martamala, B. Lukito, U. Budihusodo, L.A. Lesmana, A. Sulaiman, S. Tai, World J. Gastroenterol. 15, 4028–4036 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. N. Shinkai, Y. Tanaka, K. Ito, M. Mukaide, I. Hasegawa, Y. Asahina, N. Izumi, H. Yatsuhashi, E. Orito, T. Joh, M. Mizokami, J. Clin. Microbiol. 45, 3191–3197 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. J.M. Yuan, A. Ambinder, Y. Fan, Y.T. Gao, M.C. Yu, J. Groopman, Cancer Epidemiol. Biomark. Prev. 18, 590–594 (2009)

    Article  CAS  Google Scholar 

  43. X. Lin, X. Xu, Q.L. Huang, Y.Q. Liu, D.L. Zheng, W.N. Chen, J. Lin, World J. Gastroenterol. 11, 4703–4708 (2005)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. F. Schödel, D. Peterson, D. Milich, Intervirology 39, 104–110 (1996)

    Article  PubMed  Google Scholar 

  45. L. Barbini, L. Tadey, S. Fernandez, B. Bouzas, R. Campos, Virol. J. 9, 131 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank the staff from the Department of Virology, Sefako Makgatho Health Sciences University, for providing technical assistance. This work was supported by grants from the National Research Foundation and the Poliomyelitis Research Foundation of South Africa.

Author information

Author notes

  1. Maemu P. Gededzha

    Present address: Department of Molecular Medicine and Haematology, National Health Laboratory Service, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa

Authors and Affiliations

  1. HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Service, P.O. Box 173, MEDUNSA, 0204, Pretoria, South Africa

    Maemu P. Gededzha, Tsakani H. Sondlane, Lesibana A. Malinga, Rosemary J. Burnett, Ramokone L. Lebelo, M. Jeffrey Mphahlele & Selokela G. Selabe

  2. Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Jason T. Blackard

  3. South African Medical Research Council, Pretoria, South Africa

    M. Jeffrey Mphahlele

Authors
  1. Maemu P. Gededzha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tsakani H. Sondlane
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lesibana A. Malinga
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rosemary J. Burnett
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ramokone L. Lebelo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jason T. Blackard
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. Jeffrey Mphahlele
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Selokela G. Selabe
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MPG, LAM, RJB, JTB, MJM, and SGS designed the study. MPG, THS, LAM, JTB, and RLL performed laboratory work and/or data analysis. All authors edited the manuscript draft.

Corresponding author

Correspondence to Selokela G. Selabe.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest to declare.

Research involving human subjects

The study sample consisted of stored serum samples from HIV-positive treatment-naïve patients attending the DGMAH from 2005 to 2007. The institutional ethics review board of the University of Limpopo, Medunsa Campus (now Sefako Makgatho Health Sciences University) approved the study.

Additional information

Edited by Wolfram Gerlich.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gededzha, M.P., Sondlane, T.H., Malinga, L.A. et al. Molecular characterization of hepatitis B virus X gene in HIV-positive South Africans. Virus Genes 54, 190–198 (2018). https://doi.org/10.1007/s11262-018-1536-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11262-018-1536-5

Keywords

Search

Navigation