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Title: HIV modulation of MHC class II biosynthesis and surface expression
Author: Cresswell, Joanne
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1999
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The aim of this project was to investigate the effects of HIV infection on class II biosynthesis and surface expression on professional and non-professional APC. To investigate the mechanism by which HIV controls class II expression in non-professional APC, a transfection model was designed for the expression of the HIV env gene, either singly, or co-transfected with an HIVΔenv plasmid, in HLA-DR4+ Chinese hamster ovary (CHO-DR) cells. It was shown that the env glycoproteins produced in this model were processed correctly in both single and double transfectants, and could be incorporated into virus particles released from env/HIVΔenv transfected cells. Env production in CHO-DR cells led to an increase in the surface expression of conformationally immature class II. This increase was not due to higher levels of class II biosynthesis, or more rapid intracellular processing. This shows that, in the presence of the HIV env glycoprotein, a greater proportion of cell-associated class II reaches the cell surface, and that env may act as a chaperone, stabilising immature class II molecules. Using Western blotting, it was also shown that class II, in the form of αβ dimers, could be incorporated into virus particles released from env/HIVΔenv-transfected CHO-DR cells. It is possible that this is dependent on association with env glycoproteins, suggested by the effect of env expression on surface class II expression. The results indicate that HIV has different effects, depending on the cell type under investigation. In professional APC, class II surface expression remains unchanged despite increased biosynthesis, whilst in non-professional APC there is increased surface class II on infected cells. Data from the single, and double transfection models indicate that these effects may be mediated by the HIV env glycoprotein.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available