The importance of Nef-mediated HLA class I downregulation in HIV-1 and HIV-2 infection (360G-Wellcome-099815_Z_12_Z)
The human immunodeficiency virus (HIV) utilises a number of techniques to evade the immune system and survive in the host. HIV-1 negative factor (Nef) has previously been shown to mediate downregulation of class I human leukocyteantigen (HLA-I) molecules from the surface of cells, which is believed to facilitate evasion of cytotoxic attacks by CD8+ lymphocytes. Furthermore, HLA-B molecules are known to be more resistant to downregulation than HLA-A, whilst HLA-C is not downregulated. Studies so far have primarily used Nef derived from laboratory strains of HIV such as HIV-1SF2, rather than Nef isolated from infected patients. This project aims to explore the role of Nefin a cohort of patients with HIV-1 infection, and correlate the extent of HLA-downregulation with clinical data and progression. Nef from both elite controllers and progressors will be studied. In this cross-sectional investigation, the variability of Nef within the cohort and individual patients will be characterised, and the extent to which the protein mediates HLA-downregulation will be determined using flow cytometry. This phenomenon will also be studied in a well-characterised cohort of patients infected with HIV-2, of which very little is known regarding Nef-mediated HLA-downregulation.
£159,340 25 Jun 2012