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Gag sequences from HIV-1-infected individuals on highly active antiretroviral therapy differ from the consensus

Baars, I. (2017) Gag sequences from HIV-1-infected individuals on highly active antiretroviral therapy differ from the consensus. Master's Thesis / Essay, Biomedical Sciences.

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The latent HIV-1 reservoir in HIV-1-infected individuals undergoing highly active antiretroviral therapy (HAART) is the major barrier to curing HIV-1 infection. Recent studies suggest that these latent HIV-1 reservoirs can be eliminated by HIV-1-specific CD8+ cytotoxic T cells (CTLs) using a HIV-1-specific CTL-based vaccine. However, mutations in the latent HIV-1 reservoir form a major obstacle to this approach. Recent evidence suggests that vaccines based on CTLs stimulated with peptides of which the sequence matched that of the viruses infecting the individual were more effective than vaccines based on CTLS stimulated with consensus peptides. In addition, priming of naive CD8+ T cells with autologous HIV-1 peptides by dendritic cells (DC) was suggested to further improve effectivity. Therefore, it is hypothesised that DC-primed HIV-1-specific naive CD8+ T cells are more effective when primed with autologous Gag peptides than when primed with consensus Gag peptides. To address this hypothesis, the aim of our study was to assess the variation of HIV-1 Gag sequences in PBMCs obtained from long-term HAART-treated HIV-1-infected individuals. Nested PCR to amplify the gag gene in such individuals was successfully performed followed by Sanger sequencing. As expected, sequence differences compared to the consensus were found throughout the entire gag gene including some within the immunodominant SL9 CTL-epitope. In conclusion, we show using a newly established method for the sequencing of the gag gene, that Gag sequences from HAART-treated clade B HIV-1-infected individuals differ considerably from consensus. Our sequencing method could be used to design autologous Gag peptides. This method will therefore further help address the hypothesis that CTLs primed with autologous Gag peptides are more effective than when primed with consensus Gag peptides.

Item Type: Thesis (Master's Thesis / Essay)
Degree programme: Biomedical Sciences
Thesis type: Master's Thesis / Essay
Language: English
Date Deposited: 15 Feb 2018 08:32
Last Modified: 15 Feb 2018 08:32

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