Lentiviral accessory proteins Vpx and Vpr, viral countermeasures to host cell defences. (360G-Wellcome-108012_Z_15_Z)

The related essential lentiviral accessory proteins Vpr and Vpx are required for the optimal infection of immune cells by HIV-1 and HIV-2, the causative agents of AIDS. The function of Vpr and Vpx is to hijack the hosts protein destruction pathway to recruit cellular proteins and render the host permissive to infection. For Vpx, the cellular target is SAMHD1 a restriction factor that supresses the intracellular dNTP pool and blocks HIV-1 reverse transcription. The cellular target of Vpr is unkno wn, but introduction of Vpr into cells causes cellular arrest at a stage in the cell cycle where virus production is at the highest. Nevertheless, Vpx and Vpr are structurally conserved and exert their effects through interaction with DCAF1, a host-cell adaptor protein that directs proteins to the protein destruction machinery. We want to understand how Vpx and Vpr function at the molecular level by addressing how Vpx/Vpr interact with their cellular targets and then modify these interactions an d examine the consequences for HIV-1 infection. In the longer term, understanding the Vpx/Vpr interaction with DCAF1 will pave the way to the development of drug molecule disruptors of this host-pathogen interaction exposing the virus to the full effects of cellular defences.