Infection with the human immunodeficiency virus (HIV) constitutes a global pandemic, and South Africa forms part of the region known to house over two-thirds of HIV infected individuals worldwide. In the early stages of infection, the C-C chemokine receptor type five (CCR5) is the major HIV-1 co-receptor. The importance of this receptor in HIV infection and disease progression was recognised with the discovery of the CCR5 delta 32 (Δ32) allele. Individuals homozygous for this mutation lack functional CCR5 receptors. Consequently, they are almost completely resistant to HIV infection, while the absence of CCR5 has minimal effects on health. Heterozygous individuals display decreased cell surface CCR5 which slows disease progression. Phenotypic expression of CCR5 is heterogeneous and its relation to genetic mutations in the CCR5 gene is not currently known for the South African population. This together with the effect of CCR5 expression on HIV infection provided the rationale for investigating both the phenotypic and genotypic distribution of CCR5. The aim of this study was therefore 1) to investigate CCR5 phenotypic expression on cluster differentiation four (CD4) T-lymphocytes in a group of South African individuals and 2) to analyse the genetic variation in a South African cohort. Flow cytometric methods were used to measure the phenotypic distribution of CCR5 in 245 individuals by assessing both the percentage of CD4+CCR5+ T-cells and CCR5 density. Sixty five individuals, mostly found within the lower CCR5 receptor density range were selected for DNA sequencing. The study found considerable variability in CCR5 expression with South African individuals expressing relatively high CD4+CCR5+ T-cell percentages. Ethnicity was established as a significant variable affecting CCR5 expression with Black African individuals displaying higher (p <0.05) CD4+CCR5+ T-cell percentages and densities than Caucasians. Genotypic data revealed 70 single nucleotide polymorphisms (SNPs), four insertions and the ∆32 deletion. Results showed that Black African individuals have greater genetic diversity with 39 mutations exclusive to this group. The ∆32 mutation was not detected in the Black African group but was identified in the Caucasian group at a frequency of 18.6 %. Twelve novel mutations were identified in this study with two in the open reading frame (ORF). It is evident from the data that the variability in CCR5 phenotypic expression is difficult to correlate with specific mutations in the gene. This thesis provides information on CCR5 distribution and diversity in the South African population which will be of value to patients, clinicians and health policy officials. / Dissertation (MSc)--University of Pretoria, 2011. / Immunology / Unrestricted
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:up/oai:repository.up.ac.za:2263/31127 |
| Date | 07 August 2012 |
| Creators | Barmania, Fatima |
| Contributors | Pepper, Michael Sean, barmaniaf@gmail.com, Potgieter, Marnie |
| Publisher | University of Pretoria |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Dissertation |
| Rights | © 2011, University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. |
Page generated in 0.0019 seconds