The aim of this project is to characterize the mechanism of retroviral integration. Retroviruses efficiently and stably introduce foreign genes into the host genome. Defining the pathway and requirements for integration is significant both for the understanding of the viral life-cycle, but also as a means of introduction of DNA, in general, into mammalian cells. Two known viral components are needed for an integration event: the IN protein and the inverted repeat sequences found at the termini of the Long Terminal Repeats (LTRs). Experiments are aimed at defining the functional domains of the Moloney-Murine Leukemia Virus (M-MuLV) IN protein. A second objective is to define the specific sequences recognized by the IN protein and possibly other proteins with the LTR terminal inverted repeats. A third objective is to see if the virus could be directed to integrate into a known site in the host DNA. The information resulting from this work will give greater insight into the molecular mechanisms utilized by viruses. Such insights will obviously affect the practical concerns in using viruses as vectors.***
