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The apoptotic potential of different HIV-1 subtype C Tat mutations in cell culture
Thesis (MScMedSc)--Stellenbosch University, 2013.
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| Format: | Thesis |
| Language: | en_ZA |
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Stellenbosch : Stellenbosch University
2013
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| _version_ | 1867614123269816320 |
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| access_status_str | Open Access |
| author | Isaacs, Shahieda |
| author2 | Engelbrecht, Susan |
| author_browse | Engelbrecht, Susan Isaacs, Shahieda |
| author_facet | Engelbrecht, Susan Isaacs, Shahieda |
| author_sort | Isaacs, Shahieda |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (MScMedSc)--Stellenbosch University, 2013. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/80187 |
| institution | Stellenbosch University (South Africa) |
| language | en_ZA |
| last_indexed | 2026-06-10T12:47:00.921Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2013 |
| publishDateRange | 2013 |
| publishDateSort | 2013 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/80187 The apoptotic potential of different HIV-1 subtype C Tat mutations in cell culture Isaacs, Shahieda Engelbrecht, Susan Glashoff, Richard Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology. Medical Virology. HIV diversity Tat mutations in cell culture HIV infections -- South Africa -- Prevention Subtype C HIV infections -- South Africa -- Treatment Pathology -- Division of Medical Virology Thesis (MScMedSc)--Stellenbosch University, 2013. Bibliography The efficiency in which HIV-1 can infect, spread and evade the attack of therapeutic agents can be attributed to a high mutation rate and frequent recombination events. These factors have collectively contributed to the diversity observed in HIV-1 and resulted in a multitude of subtypes, sub-subtypes, circulating recombinant forms (CRF’s) and unique recombinant forms (URF’s). The aim of this study was to investigate HIV-1 diversity in Cape Town using a small cohort of treatment naive patients being investigated for HIV Associated Neurocognitive Disorders (HAND). Four different genomic domains: gag, pol, accessory and gp41 genes were sequenced to subtype the virus. HIV-1 tat was further investigated because the dicysteine motif has been reported to play a role in HAND. Viral RNA and proviral DNA was extracted from 64 patients and used for the amplification and sequencing of the genes. Rega and jpHMM online tools were used to identify HIV-1 subtypes and recombinants while Neighbor-joining phylogenetic trees were constructed for phylogenetic analysis. The pol gene was further investigated using SCUEAL to detect possible intra-subtype recombination and was also screened for the presence of transmitted drug resistance. In addition tat sequence datasets retrieved from the Los Alamos sequence database were investigated and compared with the newly generated sequences for the detection of point mutations and amino acid signature patterns. Sequencing identified most of the samples as subtype C; however six inter-subtype recombinants (AE, A1G, A1CU and two BC) and 9 intra-subtype C recombinants were identified. In addition 13% of pol sequences were identified with resistance mutations. Signature pattern analysis identified a high level of variability in the tat sequences: 68% were identified with C30S31; 29% with the C30C31 mutation and a single sequence with a novel mutation C30A31. Functional analysis of these mutations indicated that all mutations investigated were capable of inducing apoptosis in cell culture. The C30C31 mutation generated the highest level of apoptosis, closely followed by the C30A31 mutation. However no statistical significance could be detected between tat mutations and the observed levels of apoptosis. 2013-02-26T13:17:07Z 2013-03-15T07:39:15Z 2013-02-26T13:17:07Z 2013-03-15T07:39:15Z 2013-03 Thesis http://hdl.handle.net/10019.1/80187 en_ZA Stellenbosch University 121 p. : ill. application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | HIV diversity Tat mutations in cell culture HIV infections -- South Africa -- Prevention Subtype C HIV infections -- South Africa -- Treatment Pathology -- Division of Medical Virology Isaacs, Shahieda The apoptotic potential of different HIV-1 subtype C Tat mutations in cell culture |
| title | The apoptotic potential of different HIV-1 subtype C Tat mutations in cell culture |
| title_full | The apoptotic potential of different HIV-1 subtype C Tat mutations in cell culture |
| title_fullStr | The apoptotic potential of different HIV-1 subtype C Tat mutations in cell culture |
| title_full_unstemmed | The apoptotic potential of different HIV-1 subtype C Tat mutations in cell culture |
| title_short | The apoptotic potential of different HIV-1 subtype C Tat mutations in cell culture |
| title_sort | apoptotic potential of different hiv 1 subtype c tat mutations in cell culture |
| topic | HIV diversity Tat mutations in cell culture HIV infections -- South Africa -- Prevention Subtype C HIV infections -- South Africa -- Treatment Pathology -- Division of Medical Virology |
| url | http://hdl.handle.net/10019.1/80187 |
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