Human immunodeficiency virus type I (HIV-1) is the etiologic agent of acquired immune deficiency syndrome (AIDS). This project's long-term objective is to study the action of the HIV-1 protease to develop specific protease inhibitors that might be able to halt the viral replication. This study is possible only with the availability of large quantities of biologically active HIV-1 protease.Phase I efforts will develop a recombinant DNA system to produce the protease. The approach to be used will involve the assembly of a synthetic gene coding for the HIV-1 protease. The gene will be cloned into a plasmid and expressed in Escherichia coli. The production level of the gene product will be optimized so that the protease can be economically produced. High-level expression of the protease will enable Phase II research to focus on the E. coli fermentation scale-up, purification, and renaturation of the protease to yield biologically active HIV-1 protease.
Anticipated Results:Biologically active HIV-1 protease produced from this research will be available in large quantities to allow research for specific protease inhibitors and to study its proteolytic actions. HIV-1 protease inhibitors may be useful in halting the replication of the HIV-1 virus.National Cancer Institute
