Grant: Operating Grant - PA: HIV/AIDS Bridge Funding - Biomedical/Clinical Stream

Previous studies have suggested the existence of a new Human Immunodeficiency Virus type 1 (HIV-1) gene termed Antisense Protein (ASP). The proposed encoded protein has been difficult to detect in infected cells, and this has been a major source of concern and have contributed to the important controversy surrounding the existence of ASP. Our lab has succeeded in detecting the ASP protein by different approaches and we are confident that the ASP gene produces a protein with an important role in HIV-1 replication. In this proposal, we are interested in detecting the ASP protein in several cell types important for HIV-1 replication and in obtaining data on its possible function in cells infected by HIV-1. Through these studies, we will use some of our newly developed tools to further detect the ASP protein in cells from infected individuals. These experiments will be conducted in various cellular contexts such as mammalian cell lines and primary cells (dendritic cells, macrophages and CD4+ T lymphocytes) isolated from blood samples. The presence of the protein in infected patients will also be demonstrated by detection of specific antibodies. A series of experiments will also be designed to address the potential function played by the ASP protein. Hence, from our recent data showing the capacity of this protein to agglomerate in large complex, we will search for a possible link between the presence of the ASP protein and a cellular phenomenon termed autophagy recently shown to be important for the life cycle of the virus in macrophages. As a final objective of the current proposal, we will thus look at the impact of ASP on HIV-1 replication through its capacity to induce autophagy. Confirming the existence of a controversial viral protein in HIV-1 represents an important step in reaching a better understanding of HIV-1 replication and pathogenesis. The ASP protein might further become a new interesting target for anti-retroviral therapies.