During the process of HIV replication two viral RNAs are encapsidated into the assembling virus particle where they are found in stable but non- covalent association. Following infection of cells the RNA is converted into DNA via reverse transcription. The long term objective of this program is to understand in molecular detail the steps that result in vivo ecapsidation and dimer formation, and to understand how the structure and organization of the viral RNA influence reverse transcription. A combination of approaches are proposed to investigate RNA encapsidation, RNA dimer formation, RNA organization, and minus strand DNA synthesis during reverse transcription. We will attempt to (1) elucidate the higher order structure of the encapsidation region, (2) understand the mature of the primary dimer linkage site, 93) determine how lack of correct dimer formation leads to abrogation of replication, (4) characterize the role of nucleocapsid protein in replication and, (5) test the hypothesis that juxtaposition of the 5' and 3' ends of the RNA template are required for minus strand DNA synthesis. We hope to develop a comprehensive picture that helps us understand in and exact way how correct encapsidation and dimer formation lead to correct reverse transcription.
