Research Overview
HIV-1 ENTRY INTO CELLS: A TARGET FOR ANTIVIRAL DRUGS AND THE HUMORAL IMMUNE RESPONSE
The focus of our studies is the processes by which HIV-1 uses its envelope glycoproteins to attach to, then fuse with, its target cells, predominantly CD4-positive T-cells, macrophages and dendritic cells. Central to these early events in the viral life cycle is the involvement of the CCR5 and CXCR4 co-receptors. These proteins, whose natural function is to be G-protein coupled receptors for chemokines, provide attractive targets for the development of new generations of antiviral agents, be they conventional small molecules, antibodies or chemokines. We are working to characterize the interactions of potential inhibitors with the CCR5 and CXCR4 receptors, to better understand what will be required for successful drug development. HIV-1 attachment and entry is also the stage at which the humoral immune response interferes with viral replication, albeit rather inefficiently in the context of natural infection. Inducing an effective virus-neutralizing response by immunization would be a valuable component of a multivalent vaccine. To this end, we are using our knowledge of the structure of the HIV-1 envelope glycoproteins to develop modified forms of these proteins which we hope will elicit better immune responses than those generated during natural infection. We also wish to learn how best to present these proteins to the immune system.
