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Title: Histologic and genetic characterisation of HIV-1 infecting the lymphoid and non-lymphoid tissues in different stages of infection
Author: Wang, Ting-Huei
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2000
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The HIV epidemic continues to spread at a rate of over 6000 new infections per day. A better understanding of HIV pathogenesis and the mechanisms underlying HIV-1 related disease in specific tissues such as the brain is still a high priority in tracking the medical impact of the pandemic. This project was aimed to investigate the cellular localisation of HIV-1,cytopathology and viral phenotype variation in various organs throughout the course of HIV-1 infection. The cellular localisation of HIV-1 infection was demonstrated by immunohistochemistry, and the virus distribution, genotypes and inferred phenotype and virion diversity were determined by nucleotide sequencing. Immunohisochemistry applied in serial tissue sections or combining the double-labelling technique with various cell markers was employed to examine the variety of HIV-1 infected cell populations. During the clinical latent stage, HIV-1 p24 signal was primarily detected within lymphoid organs and few lung sections. However, in the symptomatic stage, the p24 signal was detected within a wider range of organs, including lymph node, spleen, lung, ileum, colon, liver, kidney and central nervous system. Among the lymphoid organs, p24 antigen was localised to follicle centres and intimately colocalised with CD21-positive cells follicular dendritic cells. In lung and intestine, detection of p24 antigen was confined to secondary lymphoid tissue, primarily associated with CD21-positive cells and occasionally with tissue macrophages and T-cells. In brain tissue, the HIV-1 p24 positive cells were identified as microglia and were a defining feature of HIV-encephalitis. The distributions of co-receptors CXCR4 and CCR5 were also examined by immunohistochemistry techniques in these organs. The staining patterns of CXCR4 and CCR5 positivity showed overlap. Commonly, CXCR4 and CCR5 expression was detected on neurones, epithelium cells, blood vessel endothelium cells, tissue macrophages and occasionally lymphocytes. Interestingly, in the lymphoid aggregates or lymphoid follicles, where generally p24 antigen was detected, neither CXCR4 nor CCR5 expression was detected.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available