Our laboratory focuses on understanding how HIV interacts with cellular receptors to enter cells of the immune system. Thus, we study the very earliest steps in the virus life cycle. The mechanisms by which HIV enters cells, and how this may change in infected individuals over time has importance for understanding HIV pathogenesis, the ability of HIV to establish infection in cellular reservoirs including those in the central nervous system, and the development of new HIV entry inhibitors.
- To understand how HIV establishes infection in macrophages
- To understand how HIV evolves in patients to become better able to destroy cells of the immune system
- To determine how HIV acquires resistance to CCR5 antagonists
- To elucidate the structure-function relationships of HIV envelope proteins
- To understand how certain HIV strains are able to persist in the central nervous system
- To develop novel HIV tropism assays to help physicians decide on the best treatment options for patients
- To develop and test new inhibitors of HIV entry into cells.
- The discovery, and functional consequences of the mechanism of HIV resistance to the CCR5 antagonist maraviroc
- The demonstration of alternative mechanisms of HIV engagement with either CCR5 or CXCR4 for entry into macrophages
- The characterisation of how dual-tropic (R5X4) HIV variants can establish infection within cells of the central nervous system and lymphoid tissues
- The discovery of structural determinants within the HIV gp120 proteins that expose the binding site for the cellular CD4 receptor.