Molecular characterization of hepatitis B virus X gene in HIV-positive South Africans
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.
KeywordsHepatitis B virus (HBV) HIV South Africa Africa Genotype HBx
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.
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.
Compliance with ethical standards
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.
- 1.World Health Organization. Hepatitis B fact sheetGoogle 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)CrossRefPubMedGoogle 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)CrossRefPubMedGoogle 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
- 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)CrossRefPubMedPubMedCentralGoogle Scholar