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Title: Genetic analysis of populations of HIV-1 variants infecting different tissues in vivo
Author: Hughes, Elizabeth S.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1997
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The time of spread of HIV-1 to non-lymphoid tissue was investigated by sequence comparisons of variants infecting a range of tissues from three individuals with AIDS in the p 17gag gene, and flanking regions of V1/V2. Phylogenetic analysis revealed several lineages in each individual that contained sequences from lymphoid and nonlymphoid tissue, such as brain, in both regions. This observation contrasts strongly with the previously described organ-specific sequences in the V3 region in this study population and other investigations. By estimating mean synonymous pairwise distances in the p 17gag region, we were able to calculate the time of divergence of variants infecting lymphoid and non-lymphoid tissues, such as brain. In lymphoid tissue the mean diversity of gag sequences implied an approximate population age of 2.65 to 5.6 years, while those infecting brain were significantly more variable, suggesting an even earlier time of diversification (4.1 to 6.2 years). In two of the three individuals, these times of divergence indicate that infection of the brain may have occurred as an early event in the progression to disease, preceding the onset of AIDS by several years. This is the first report where it has been possible to estimate times of diversification in different tissues in vivo and is of importance in understanding the dynamics of the spread of HIV-1 into non-lymphoid tissue, and its possible adaptation for replication in different cell types. In summary, both analysis of the P17gag and V1/V2 regions revealed high levels of heterogeneity of HIV-1 in tissue such as brain producing multiple lineages upon phylogenetic analysis. We have therefore found no evidence for specifically neurotropic variants of HIV-1 and question the idea that spread into the central nervous system or other non-lymphoid tissues requires specific adaptation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available