Regulation of retroviral latency in the human genome.

The regulation of retroviral latency and expression is a problem of central importance in naturally retrovirus infections such as HIV-1 and human T-lymphotropic virus type 1 (HTLV-1) and in gene therapy with retroviral vectors. In this programme I will exploit our recent exciting discoveries and the unique advantages of HTLV-1 infection to answer fundamental questions on the regulation of retroviral targeting and latency in natural infection in humans and both in vivo and in vitro with newly de veloped lentiviral gene therapy vectors. I will use the state of the art techniques my group has developed over the last three years, comprising novel high-throughput mapping and analysis of proviral integration sites in vivo and mechanistic experiments in vitro. The results will have both scientific and clinical significance in pathogenic human retroviral infections and in the rapidly developing field of gene therapy. The key goal is to identify the mechanisms by which HTLV-1 regulates its la tency in vivo and so persists in the face of a strong host immune response, causing fatal and disabling diseases for which there is no effective treatment.