The role of envelope proteins in the outcome of lentivirus infections in hominoids (360G-Wellcome-082874_Z_07_Z)

The overall aim of the project is to better characterise the non-pathogenic HIV-1 and SIVcpz infection of chimpanzees, where a high viral load is maintained without progression to AIDS, and to determine the factors that result in this non-progressive outcome. Determining the differences between pathogenic infection of humans and non-pathogenic infection of our closest relative will provide unique insight into the pathogenesis of HIV-1 infection, which remains poorly understood after over 25 years of research. Key differences described so far are that non-pathogenic infection of chimpanzees does not result in chronic immune activation or NK cell dysfunction shown in pathogenic infections of humans. In both of these phenomena, the majority of effected cells are not infected, suggesting a viral protein can induce these effects independently of cellular infection. Viral envelope on the viral surface, or in a soluble form following shedding, can interact with a number of receptors. Interactions with NK-cells and HIV-1 envelope leads to NK-cell dysfunction, and interaction with T -cells can induce virological synapses, a structure similar to the immune synapse involved in T-cell activation. This project will focus on immune dysfunction resulting from direct interactions between HIV-1/SIVcpz envelope and cells of the immune system purified from cryopreserved human and chimpanzee PBMCs.