Grant: Operating Grant - PA: HIV/AIDS Research Initiative - Biomedical/Clinical Stream

Retroviruses such as human immunodeficiency virus type 1 (HIV-1), which is the cause of acquired immunodeficiency syndrome (AIDS), infect cells by integrating their viral DNA into the host genome. A protein called HIV-1 "integrase" is required for insertion of HIV-1 viral DNA into the genome, a process that also requires host proteins. We are using the model system budding yeast to study which host proteins are required for targeting retroviral DNA into the genome. Ty1 retrotransposons, which integrate into the yeast genome, are similar in structure and lifestyle to retroviruses. We have made the exciting discover that Ty1-integrase, which is conserved with HIV-1 integrase, interacts with a protein called separase. Separase is well known for its conserved role in mediating separation of chromosomes during mitosis by cleaving cohesin, which we have found also interacts with Ty1-integrase. In this proposal, we will determine how separase and cohesin target Ty1-integrase to the yeast genome. Understanding the basic mechanisms of viral integration will help design antiviral integrase inhibitors which is important for clinical applications.