Human Immunodeficiency Virus (HIV) is a virus that causes Acquired Immunodeficiency Syndrome (AIDS). Although it is one of the most studied viruses, no completely effective treatment or vaccine exists. Viral protein R (Vpr) is a multifunctional accessory protein that plays an important role in pathogenesis and replication in HIV, and it is believed to be a potential target for therapeutic intervention. Polymorphisms of Vpr have been shown to relate to dramatic variations in the development rate of AIDS. The Vpr mutants R36W and R77Q are associated with Rapid Progressor (RP) and Long Term Non Progressor (LTNP) phenotypes, respectively. Regular AIDS onset is 5-7 years for wild type (WT) virus, 3-5 years for patients with the RP Vpr mutant, and 10 or more years for the LTNP mutant. We have successfully shown that R36W enhances the ability for HIV to replicate, and it primarily relies on necrotic, highly inflammatory pathways for cell death. R77Q activates G2 cell cycle arrest more efficiently followed by apoptosis, a death mechanism with less inflammation. While the molecular mechanism of Vpr-induced apoptosis is known, it is not yet determined why point mutations in Vpr are changing apoptosis levels. HIV progresses into AIDS by depleting CD4+ helper T cells via chronic immune activation and inflammation, so we started investigating the mechanisms by which the Vpr mutants change apoptosis levels by looking at release of inflammatory cytokines. We choose to quantify levels of IL-6, IL-10, IL-1β, TNF-α, and Type 1 IFN-α through a cytometric bead array. We saw that R77Q under-expresses pro-inflammatory cytokines, such as IL-6 and TNF-α, compared to WT and R36W. We also saw that R77Q has significantly higher expression of IL-10, an anti-inflammatory cytokine, compared to R36W. These results match our predictions and show that Vpr polymorphisms are related to inflammatory cytokines and immune activation. Functions of Vpr come from binding and modifying cellular proteins and enzymes. We will continue researching what molecular interactions change between Vpr mutants to better understand shifts in apoptosis levels. Vpr can be found intracellularly in the nucleus, cytoplasm, and mitochondria and extracellularly in secreted proteins and within virions. We plan to execute an experiment determining where Vpr is most concentrated by isolating these intracellular and extracellular components individually and using Western Blots to analyze the proteins contained in the samples. We hypothesize that differences in Vpr concentrations exist among Vpr mutants both intracellularly and extracellularly. Since bystander cells not infected by HIV were also found to be apoptotic, we also hypothesize that extracellular, secreted Vpr could be inducing this phenomenon. Through these experiments, we aim to discover more about the role Vpr plays in cell death by apoptosis and contribute to the existing literature exploring the importance of Vpr.