Diversity within the Immunodominant Epitopes of Envelope gp41 HIV-1 in Kenya and Its Effects on Performance of the HIV-1 Antibody-Based Detection Kits
American Journal of Internal Medicine
Volume 3, Issue 1, January 2015, Pages: 15-22
Received: Jan. 22, 2015;
Accepted: Feb. 2, 2015;
Published: Feb. 10, 2015
Views 2334 Downloads 114
James Kimotho, Kenya Medical Research Institute, Nairobi, Kenya
Zipporah N g’ang’a2, South Eastern Kenya University, School of Pure and Applied Science, Kitui, Kenya
Edna Nyairo, Kenya Medical Research Institute, Nairobi, Kenya
Missiani Ochwoto, Kenya Medical Research Institute, Nairobi, Kenya
Nicholas Nzioka, Kenya Medical Research Institute, Nairobi, Kenya
Francis Ogolla, Kenya Medical Research Institute, Nairobi, Kenya
Michael Kiptoo, Kenya Medical Research Institute, Nairobi, Kenya
Background: Human Immunodeficiency Virus (HIV) is characterized by high rates of genetic variability in vivo that could affect the performance of the HIV-1 Antibody-Based Detection Kits in use in Kenya. Objective: This study aimed at establishing the diversity of Envelope gp41 Epitopes and its effects on performance of the currently used HIV diagnostic kits in Kenya. Methods: Two hundred (200) HIV positives and 200 HIV negatives samples were collected from the Regional Blood Transfusion Centers (RBTCs) in Kenya. Viral RNA was extracted from 96 HIV Positive samples and sequenced on gp41-immunodominant region (IDR).The sequences obtained were analyzed using various applications in the Los Alamos HIV Database. The HIV gp41-IDR consensus sequence generated was used to synthesize gp41 IDR peptide. The Global HIV gp41-IDR Consensus nucleotide sequence was obtained from literature and used also to synthesis corresponding gp41 IDR peptide. The two peptides were used to prepare HIV Testing ELISA kits. The400 plasma samples that had been collected from this study from RBTCs were tested using five HIV testing kits approved for use in Kenya. The same samples were tested using the two ELISA system developed. Results: The HIV Consensus gp41-IDR peptide from Kenya displays a similarity of 93.0% against HXB2 sequence and 95.3% against Global HIV Consensus gp41-IDR amino acid sequence. There were 331 (7.8%) substitutions in the Consensus gp41-IDR peptides (Kenya) out of which 151substitutions were due to the substitution in positions A96→N (n = 79) and A101→S (n = 75). Both Consensus gp41-IDR peptides (Kenya) and Consensus gp41-IDR peptides (Global) showed common substitutions rate of 4.2% (n = 151). All the kits that were used showed 100% agreement in results. Conclusion: Although the HIV Consensus gp41-IDR peptides (Kenya) showed marked substitutions in respect to Consensus gp41-IDR peptide (Global) there was no difference in effects on the performance of the HIV-1 Antibody-Based Detection Kits in use in Kenya.
Zipporah N g’ang’a2,
Diversity within the Immunodominant Epitopes of Envelope gp41 HIV-1 in Kenya and Its Effects on Performance of the HIV-1 Antibody-Based Detection Kits, American Journal of Internal Medicine.
Vol. 3, No. 1,
2015, pp. 15-22.
UNAIDS. (2013). AIDS epidemic update: December 2013.
National AIDS and STI Control Programme, Ministry of Health, Kenya. September 2013. Kenya AIDS
Hutchinson, J. A. (2009). The Biology and evolution of HIV. Annual Review of Anthropology, 30, 5-108.
Lihana, R. W; Khamadi, S.A.; Lwembe, R. M.; Ochieng, W.; Kinyua, J.G.; Kiptoo, M. K.; Muriuki, J. K.; Lagat, N.; Osman, S.; Mwangi, J. M.; Okoth, F. A. and Songok E.M. (2009). The changing trend of HIV type 1 subtypes in Nairobi. AIDS Research and Human Retroviruses, 25, 337-42
Temin H. (1993). Retrovirus variations and reverse transcription: Abnormal strand transfers results in retrovirus genetic variation. Proceedings of the National Academy of Sciences, 90, 6900-3.
Wain-Hobson, S. (1999). Multiple infected cells and rampant recombination 6th Annual International Discussion Meeting on HIV Dynamics and Evolution; Atlanta
Holland, D. E. (1994). Mutation rates and rapid evolution of RNA viruses. In: The evolutionary biology of viruses. Morse, S.S. (ed).New York, Raven Press, 161- 85
Wei, X.; Liu, X.; Dobbs, T.; Kuehl, D.; Nkengasong, J.; Hu, D.; and Bharat Parekh, B. (2010). Development of Two Avidity-Based Assays to Detect Recent HIV Type 1 Seroconversion Using a Multisubtype gp41 Recombinant Protein. AIDS Research and Human Retroviruses, 26(1), 61-71. http://online.liebertpub.com/doi/abs/10.1089/aid.2009.0133. Accessed on 31st Dec 2014.
Thorstensson, R.; Andersson, S.; Lindbaeck, S.; Dias, F.; Mhalu, F.; Gaines, H. and Biberfeld, G. (1998) Evaluation of 14 commercial HIV-1/HIV-2 antibody assays using serum panels of diﬀerent geographical origin and clinical stage including a unique sero-conversion panel. Journal of Virological Methods, 70, 139-151.
Masciotra, S.; Rudolph, D. L.; Der Groen, G. V.; Yang, C and Lal.R.B. (2000). Serological Detection of Infection with Diverse Human and Simian Immunodeﬁciency Viruses Using Consensus env Peptides. Clinical and Diagnostic Laboratory Immunology, 7(40), 706–709
Bártolo and Taveira. (2012). HIV-1 Diversity and Its Implications in Diagnosis, Transmission, Disease Progression, and Antiretroviral Therapy. www.intechopen.com/download/pdf/28892. Accessed on 2nd Dec 2014
Ho, D; Neumann, A; Perelson, A; Chen, W; Leonard, J.M. and Makowitz, M. (1995). Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature, 373, 123-6
Kenya National Bureau of Statistics. (2010). HIV/AIDS-Related Knowledge, Attitudes, And Behaviour, Kenya Demographic and Health Survey (KDHS) 2008-09, 173-207.
http://www.measuredhs.com/pubs/pdf/FR229/FR229.pdf. Accessed on 2nd Dec 2014
Horal, P.B.; Svennerholm, S.; Jeansson, L.; Rymo, W. W.; Hall,and A.Vahlne. (1991). Continuous epitopes of the human immunodeﬁciency virus type 1 (HIV-1) transmembrane glycoprotein and reactivity of human sera to synthetic peptides representing various HIV-1 isolates. J. Virol. 65:2718–2723.
Oldstone, M. B.; A. Tishon, H.; Lewicki, H. J.; Kyson, V. A.; Feher, N.; AssaMunt and P. Wright, E. (1991). Mapping the anatomy of the immunodominant domain of the human immunodeﬁciency virus gp41 transmembrane protein: peptide conformation analysis using monoclonal antibodies and proton nuclear magnetic resonance spectroscopy. J. Virol. 65:1727–1734.
Parekh BS, Hu DJ, Vanichseni S, Satten GA, Candal D. (2001) Evaluation of a sensitive/less-sensitive testing algorithm using the 3A11-LS assay for detecting recent HIV seroconversion among individuals with HIV-1 subtype B or E infection in Thailand. AIDS Res Hum Retroviruses 17: 453–458.
Young CL, Hu DJ, Byers R, Vanichseni S, Young NL. (2003) Evaluation of a sensitive/less sensitive testing algorithm using the bioMerieux Vironostika-LS assay for detecting recent HIV-1 subtype B’ or E infection in Thailand. AIDS Res Hum Retroviruses 19: 481–486.
Johnson, R. P., A. Trocha, T. M. Buchanan, and B. D. Walker. 1992. Identificationof overlapping class I-restricted cytotoxic T cell epitopes in a conserved region of the human immunodeficiency virus type 1 envelope glycoprotein: definition of minimum epitopes and analysis of the effects of sequence variation. J. Exp. Med. 175:961–971.