The objective of the project is to understand the role of the centrosome in the life cycle and assembly process of the human immunodeficiency virus (HIV), the causative agent of AIDS. The aims are to delineate the viral and host factors, which define this interaction and to seek promising drug targets for novel antiviral approaches to HIV. A number of stages in the HIV life cycle are currently targeted for therapeutic attack. As yet, none of these involve the virus assembly process or the subcellular trafficking pathway. Recent evidence concerning early stages of assembly implicates the centrosome of the cell and some highly conserved viral components. The methods involved will be in vivo imaging, including selected mutants of the virus, and genetic and biochemical analyses. These latter will involve RNA analysis, subcellular fractionation of centrosomes, proteomic profiling and mass spectrometry to identify proteins interacting with the virus. The study is highly relevant since the AIDS epidemic continues to spread globally and there is no evidence of a vaccine as yet. Despite a number of good antiviral drugs, these can only control and not eliminate the virus and there is growing evidence of viral resistance to the currently available drugs and a significant level of patient intolerance to these. Thus, there is an urgent need for more therapies targeting different stages of the viral infection. The work will contribute to health and wealth creation in the European Union by improving its scientific research base and opening up new translational targets. It will also, ultimately, contribute to global improvements in health, especially in the developing world where the AIDS epidemic is most serious.
Fields of science
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