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Title: A comparison of the effects of HIV-1 and HIV-2 infection on T lymphocyte turnover and their relationship to immune activation
Author: Hegedus, Andrea
Awarding Body: St George's, University of London
Current Institution: St George's, University of London
Date of Award: 2013
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HIV -2 represents a natural model of attenuated HIV infection. Although capable of inducing AIDS, most patients maintain healthy CD4 counts and undetectable viral loads throughout their lives. However, once patients have progressed to AIDS, characterised by high viral loads, they show similar symptoms to those with HIV-l infection. We hypothesized that HIV-2 with low/undetectable viral load would not significantly affect Iymphocyte turnover and immune activation, compared to healthy controls, while HIV -2 with high viral load would accelerate turnover rate and increase immune activation in a pattern similar to HIV-l. Lymphocyte turnover was measured by in vivo deuterated glucose labelling, naive (CD45RA+) and memory (CD45RO+) CD4+ and CD8+ T Iymphocytes sorted magnetically. Proliferation rates were derived from modelling deuterium enrichment in DNA, measured by gas chromatography/mass spectrometry. Immune activation markers HLA-DR and CD38 were measured by ex vivo immunostaining and T cell receptor excision circle (TREC) content by real-time PCR. The pattern of accelerated turnover was similar in HIV -2 with high viral load and HIV - I and affected CD8+ more than CD4+ cells and memory more than naive cells. Turnover in HIV-2 low viral load subjects was comparable to controls. These kinetic findings paralleled markers of immune activation; CD4 lymphopenia, viral load 'and immune activation all correlated with turnover of both CD4+ and CD8+ memory cells but the strongest association was with immune activation. Reduced TREC content was also a feature in HIV -2 infection, especially in high viral load subjects. Mathematical modelling revealed that HIV -2 infection had different effect on CD4+CD45 RA + cells than did HIV - I infection. We can conclude that low levels of immune activation may be pivotal in determining the relatively benign outcome in HIV-2 infection. Kinetically, HIV-2 is dichotomous with high • viral load subjects showing a pattern of activation, accelerated turnover and progression similar to HIV - I infected subjects. 3
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available