No description available.

Thesis (PhD (Pathology. Medical Virology))--Stellenbosch University, 2006. / Host susceptibility to human immunodeficiency virus-1 (HIV-1) infection and disease progression to acquired immunodeficiency syndrome (AIDS) varies widely amongst individuals. This observation led to the identification of host genetic factors playing a vital role in HIV-1 pathogenesis. Previous studies mainly focusing on Caucasian-based populations have indicated possible associations between genetic variants and host susceptibility to HIV-1/AIDS. The limited studies performed on African-based populations have emphasised the need for extensive investigation of both previously reported and particularly novel genetic variants within the older and genetically diverse Sub-Saharan African populations. In this study, the case-control samples were represented by African individuals of Xhosa descent, all residing in the Western Cape Province of South Africa. This included 257 HIV-1 seropositive patients and 110 population-matched HIV-1 seronegative controls. Mutational screening was performed in a subset of individuals for the entire coding regions of the CC chemokine receptor 5 (CCR5) and CC chemokine receptor 2 (CCR2) genes, and the 3’ untranslated region of the CXC chemokine ligand (CXCL12) gene, as previously reported (Petersen, 2002). Further analysis of these genes in a larger study sample involved the genotyping of previously identified mutations and single nucleotide polymorphisms (SNPs), which forms part of the present study. In addition, mutational screening was performed for the entire coding region of the CXC chemokine receptor 4 (CXCR4) gene, partial coding region of the mannose binding lectin (MBL) gene, and the promoter regions of interleukin 4 (IL4), interleukin 10 (IL10) and the solute carrier 11A1 (SLC11A1) genes. This was followed by genotyping of SNPs occurring in CCR5, CCR2, CXCL12, MBL, IL4, IL10, CX3C chemokine receptor 1 (CX3CR1), CC chemokine ligand 5 (CCL5) and tumour necrosis factor alpha (TNFα) genes. Significant associations were observed with HIV-1 susceptibility in the Xhosa population of South Africa. These included the CCR5-2733A>G, CX3CR1V249I, IL10-819C>T and IL10-592C>A SNPs being associated with a reduced risk for HIV-1 infection, while the CCR5-2135C>T and SDF1-3’G>A (CXCL12-3’G>A) SNPs were associated with increased susceptibility to HIV-1 infection. Furthermore, certain haplotypes for IL4 and IL10 showed association with reduced risk for HIV-1 infection. This included the identification of a novel IL4 haplotype restricted to the HIV-1 seronegative control group. This study emphasises the importance of considering genetic diversity across all populations, as certain HIV-1/AIDS associations appear to be restricted to specific ethnic groups. These findings have also provided an understanding for further elucidating the functional roles of genetic variants in determining HIV-1/AIDS susceptibility. Ultimately, such genetic association studies will contribute to establishing HIV-1/AIDS risk profiles for African-based populations from pandemic-stricken Sub-Saharan Africa.

<p>Over the past two decades of HIV research, effective vaccine candidates have been elusive. Traditionally viral research has been characterized by a gene -by-gene approach, but in the light of the availability of complete genome sequences and the tractable size of the HIV genome, a genomic approach may improve insight into the biology and epidemiology of this virus. A genomic approach to finding HIV vaccine candidates can be facilitated by the use of genome sequence visualization. Genome browsers have been used extensively by various groups to shed light on the biology and evolution of several organisms including human, mouse, rat, Drosophila and C.elegans. Application of a genome browser to HIV genomes and related annotations can yield insight into forces that drive evolution, identify highly conserved regions as well as regions that yields a strong immune response in patients, and track mutations that appear over the course of infection. Access to graphical representations of such information is bound to support the search for effective HIV vaccine candidates. This study aimed to answer the question of whether a tool or application exists that can be modified to be used as a platform for development of an HIV visualization application and to assess the viability of such an implementation. Existing applications can only be assessed for their suitability as a basis for development of an HIV genome browser once a well-defined set of assessment criteria has been compiled.</p>

<p>Over the past two decades of HIV research, effective vaccine candidates have been elusive. Traditionally viral research has been characterized by a gene -by-gene approach, but in the light of the availability of complete genome sequences and the tractable size of the HIV genome, a genomic approach may improve insight into the biology and epidemiology of this virus. A genomic approach to finding HIV vaccine candidates can be facilitated by the use of genome sequence visualization. Genome browsers have been used extensively by various groups to shed light on the biology and evolution of several organisms including human, mouse, rat, Drosophila and C.elegans. Application of a genome browser to HIV genomes and related annotations can yield insight into forces that drive evolution, identify highly conserved regions as well as regions that yields a strong immune response in patients, and track mutations that appear over the course of infection. Access to graphical representations of such information is bound to support the search for effective HIV vaccine candidates. This study aimed to answer the question of whether a tool or application exists that can be modified to be used as a platform for development of an HIV visualization application and to assess the viability of such an implementation. Existing applications can only be assessed for their suitability as a basis for development of an HIV genome browser once a well-defined set of assessment criteria has been compiled.</p>