HIV-1 Vpr Induces DNA Replication Stress Via the Ubiquitin Proteasome System

Human Immunodeficiency Virus Type-1 (HIV-1) destroys the immune system of infected individuals, and is responsible for over 20 million deaths worldwide. The immune deficiency observed in infected individuals is due to direct viral infection and killing of CD4+ T cells. Several virus-encoded gene products have been implicated in CD4+ T cell killing. The vpr gene product has been demonstrated to have several effects on CD4+ T cell biology, including cell cycle arrest in G2 phase and subsequent apoptotic cell death. The research described in this dissertation focuses delineating the molecular mechanism by which Vpr induces G2 arrest.