The purpose of this research project is to study thoroughly the molecular and biological properties of two proteins that play key roles in the life cycle of human immunodeficiency virus (HIV-the AIDS virus). The first is the enzyme RNA-dependent DNA polymerase (reverse transcriptase-RT), and the second is the integration protein. These proteins are involved in the process of transcribing the viral RNA into DNA and in the subsequent integration of the viral DNA into the hose genome. The gene segments encoding these proteins were cloned by us in E. coli expression vectors. Bacterial strains that contain these expression plasmids produce substantial amounts of the two proteins. Both proteins closely approximate the corresponding viral proteins in the primary amino acid sequence. Purification from the bacteria of large amounts of these HIV proteins (which, at least in the case of RT, have been shown to be fully enzymatically active) will allow detailed biochemical and structural studies and provide a clearer understanding of the functions of the proteins. The information obtained should be useful in screening and designing drugs that inhibit the activities of the proteins, and should be helpful in the development of new drugs effective against AIDS. The E. coli system is suitable for the generation of mutations of the HIV proteins and the subsequent analyses of the effects of these mutations on the catalytic activities and drug sensitivity of the proteins. We propose to generate and screen for mutations of RT that might evade the present drugs used against AIDS, which could be helpful in developing drugs effective against mutated forms of HIV RT that might arise in the future.