Lentiviral accessory proteins Vpx and Vpr, viral countermeasures to host cell defences

Vpr and Vpx are essential lentiviral accessory proteins required for optimal infection of immune cells by HIV-1 and HIV-2, the causative agents of AIDS. The function of Vpr and Vpx is to implement the destruction of host-cell defence proteins that would otherwise inhibit virus replication and so render the host permissive to infection. Both Vpx and Vpr exert their effects through interaction with DCAF1, a host-cell adaptor protein that directs proteins to the cell's E3 ligase ubiquitination machinery. Using their combined strengths in structural biology, retrovirology and cell biology, Dr Stoye and Dr Taylor propose to investigate how Vpx and Vpr interact with their cellular targets and examine the consequences for HIV-1 infection upon modification or disruption of these interactions. Such studies are prerequisites to the development of drug molecule ‘disruptors’ of this host-pathogen interaction that target viral countermeasures and expose the virus to the full effects of cellular defences.