Characterisation of a novel human T-cell lymphotropic virus integrase binding partner: from structure to function

The delta-retrovirus human T-cell lymphotropic virus type 1 (HTLV-1) is the cause of an aggressive T-cell leukaemia and a debilitating neurological disease. To date, there are no effective treatments. One unique and essential step in the life cycle of retroviruses such as HTLV-1 is the integration of a DNA copy of the viral RNA into the host genome. This process is catalysed by the viral enzyme integrase. Target site selection is not random, but appears to be determined by the interaction between integrase and a host factor. Recent findings suggest a correlation between integration into active transcription units, increased proviral expression and development of disease. Using a proteomics screen Dr Maertens's group has identified a set of HTLV-1 integrase binding partners, of which one candidate also significantly stimulates the HTLV-1 integrase biologically relevant activity. During this award the group’s main aims are to define the mechanism for modulation of IN activity by this novel host factor, to characterise the role of the integrase binding partners in HTLV-1 infection, and to structurally characterise the delta-retroviral integration machinery. This study will also inform the design and development of drugs to treat HTLV-1-infected patients.