Retroviruses integrate a DNA copy of their genome into host DNA as an obligatory step in their replication cycle. Our work focuses on the molecular mechanism of integration. The enzyme involved in the integration process is the virus encoded integrase protein. Our recent studies have focussed on the interaction of viral DNA substrate with the active site of HIV integrase. We are also studying the interaction of inhibitors with the active site of HIV integrase. A collaboration has been established with Shionogi Co, Ltd and the Davies laboratory in LMB to study the structure of integrase-inhibitor complexes. Structures obtained to date reveal the mode of binding of the Shionogi inhibitors to the active site. We are also studying a novel cellular protein (BAF) that is involved in preventing self-destructive autointegration of retroviral DNA. This protein is highly conserved throughout higher eukaryotes and is a major DNA binding activity in the cytoplasm. Our current model is that it blocks autointegration by bridging together segments of the viral DNA resulting in intramolecular compaction, rendering the viral DNA inaccessible as a target. BAF forms a defined complex with DNA that comprises a dodecamer of BAF associated with six DNA segments. Inhibitory RNA experiments in collaboration with Mike Krause in LMB reveal a mitotic defect when BAF in inhibited in C.elegans. The precise role of BAF for the host cell is currently under investigation. - Retrovirus HIV DNA integration integrase BAF autointegration