Study of retroviruses has led to major advances in fundamental biology including the discovery of oncogenes and the modification of the central dogma. In this spirit, we investigate the mechanisms of HIV-1 transmission, replication, pathogenesis, and immunity, with the goal of advancing understanding of the basic workings of the cell. The simplicity of the HIV-1 genome renders the virus dependent upon host cell machinery at each step in the virus life cycle. Pathology associated with HIV-1 infection necessarily results from a finite set of interactions among cellular factors and the nine total HIV-1 genes. By developing and applying genetic and biochemical screens we attempt to identify cellular factors of functional relevance to the virus and, more generally, to cellular physiology. In effect, we exploit HIV-1, using the virus to elucidate mechanisms of cell cycle progression and cytokinesis, transcriptional regulation, genetic recombination, pluripotency, signal transduction, and cytokine expression, as well as protein folding and antigen presentation. Our research is basic in nature but by shedding light on mechanisms of HIV-1 replication and immune system evasion we hope to contribute to the development of therapeutics and vaccines that target this virus, as well as seemingly unrelated diseases such as cancer, asthma, and diabetes. All of our research has been conducted with students and postdocs in an academic setting and has been continuously funded by the NIH since 1990, as well as by the European Union, the Swiss National Fund, and a number of private foundations.