The overall objective of the proposed research is to elucidate the mechanisms by which transcriptional regulation influences the cell tropism of retroviruses. As a model system, the P.I. is studying the contribution of the transcriptional enhancer of a replication competent mouse retrovirus, the Moloney murine leukemia virus. There are multiple binding sites for host nuclear transcription factors on the Moloney virus enhancer. One of these binding sites, the Leukemia Virus fact b (LVb) site is the most highly conserved sequence in the enhancers of mammalian type C retroviruses. There is indication that a protein(s) that binds the LVb site contributes significantly to the pathogenesis of the Moloney virus. Dr. Speck plans to characterize, purify and obtain molecular clones encoding the nuclear DNA-binding protein that binds to the LVb site in the Moloney virus enhancer, and most likely to the enhancers of many mammalian C-type retroviruses.