Interferon and MX2 Mediated Control of HIV-1. (360G-Wellcome-106223_Z_14_Z)

The outcome of viral infection is determined by competition between the virus and its host, and in particular the balance between host-encoded dependency factors whose exploitation promote virus growth, and immune and inflammatory responses that control infection yet may also exacerbate disease pathology. Here, we outline experiments: to understand the principles that underpin the recently discovered capacity of the type-1 interferon (IFN) inducible protein MX2 (myxovirus resistance 2, or MXB) to inhibit human immunodeficiency virus type-1 (HIV-1) infection; to identify additional, novel interferon stimulated genes (ISGs) that regulate HIV-1 replication and to define their functions; and, to explore further the dynamic interplay between type-1 IFN and HIV-1 in the context of natural human infection. We will employ a collaborative and multi-disciplinary approach, blending virological, molecular genetic, cell biological, biochemical and structural biology methodologies, with the analys es of viral isolates and specimens from patients and informative interventional trials. Four inter-related Aims are proposed: Aim 1. Delineating MX2 structure-function Aim 2. MX2 interactions with cell and viral factors Aim 3. Screening for novel anti-viral ISGs Aim 4. Learning from viral evolution and in vivo interventions