eprintid: 10119647
rev_number: 8
eprint_status: archive
userid: 638
dir: disk0/10/11/96/47
datestamp: 2021-01-21 15:08:12
lastmod: 2021-01-21 15:08:12
status_changed: 2021-01-21 15:08:12
type: thesis
metadata_visibility: show
creators_name: Ait-Khaled, Mounir
title: Sequence analysis of human immunodeficiency virus type 1: A cross-sectional and longitudinal analysis
ispublished: unpub
keywords: Biological sciences; HIV-1
note: Thesis digitised by ProQuest.
abstract: The replication of HIV-1 and the turnover of CD4 cells in vivo is a highly dynamic process. This environment of continuous de novo virus infection and extensive replication provides an ideal setting for the generation of HIV-1 variants. The objectives of this thesis were to perform a cross-sectional and longitudinal sequence analysis of HIV-1 in blood and multiple tissues of HIV-1 infected individuals. Five to 20 clones of Polymerase Chain Reaction (PCR) amplicons were sequenced and their relationships investigated using phylogenetic methods. An analysis of V3 sequences from a patient at the time of seroconversion revealed a homogeneous quasispecies which contrasted with the high diversity observed in the V3 quasispecies from a patient with AIDS. Phylogenetic analysis of HIV-LTR variants from LN and blood from 4 patients revealed 2 distinct patterns. First, an independent clustering of LN and PBMC variants, indicating a compartmentalisation of the two quasispecies for the patient with an intact lymph node. Second, non-polarised trees with variants from either LN or PBMC present in common branches for the patients with a disrupted LN architecture. These results suggest that the lymph nodes may be important in the sequestration/evolution of distinct HIV-1 variants. A similar phylogenetic analysis has been carried out on LTR variants from multiple postmortem samples (spleen, lung, spinal cord, ganglion, lymph node and blood) of a patient who died with AIDS. The results revealed a genetically distinct LTR quasispecies in the nervous tissues compared to that present in the other tissues. The nervous tissue quasispecies was characterised by 7 mutations in the normally conserved TAR region which would be expected to abrogate tat transactivation. However, this quasispecies showed the maintenance of prototypic NF-kB sites which would allow TAR independent kB tat transactivation to occur. These data provide evidence for a role of the LTR in the adaptation of HIV-1 to the nervous tissue environment by optimising the use of specific cellular transcription factor(s).
date: 1996
oa_status: green
full_text_type: other
thesis_class: doctoral_open
thesis_award: Ph.D
language: eng
thesis_view: UCL_Thesis
primo: open
primo_central: open_green
verified: verified_manual
full_text_status: public
pages: 275
institution: UCL (University College London)
department: Virology
thesis_type: Doctoral
citation:        Ait-Khaled, Mounir;      (1996)    Sequence analysis of human immunodeficiency virus type 1: A cross-sectional and longitudinal analysis.                   Doctoral thesis  (Ph.D), UCL (University College London).     Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10119647/1/out.pdf