CHARACTERIZATION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE-1 (HIV-1) VIRAL PROTEIN R (VPR) DURING DISEASE PROGRESSION AND PATHOGENESIS

Human immunodeficiency virus (HIV), which progresses into the disease commonly referred to as Acquired Immunodeficiency syndrome (AIDS), has become one of the world’s most destructive epidemics since its discovery in the early 80's. To date, the virus has killed more than 25 million people, with an average of 5 million newly infected cases last year alone. The HIV-1 genome is comprised of structural and enzymatic polyproteins as well as regulatory/accessory, which are essential for viral replication. Viral protein R (Vpr), which is identified as one of the regulatory/accessory genes, is responsible for carrying out several of the virus' life functions, including virus replication, cell cycle regulation, apoptosis, and immune dysregulation. Through research of the virus, the disease has been divided into two very distinctive categories: Rapid Progressors (RPs) and Long Term Non-Progressors (LTNPs). The differences between these categories are due to the varying quasispecies, which infect the population, and ultimately disease progression. Several well-known mutations that occur within vpr have been associated with disease progression, linking them to one of the category types. Using a population from the Multicenter AIDS Cohort Study (MACS), patient vpr genotypes were analyzed and compared with current findings in research. Several of the patients' deduced amino acid sequences revealed different gene variants, truncations, as well as a number of point mutations. Functional analysis revealed a decrease in cell apoptosis, which could have been caused by the observed point mutations. Further analysis is needed in order to determine if any other functions of the virus are disrupted due to the observed mutations. Because the virus has the ability to make changes within, as of right now the only hope in counteracting the effects of HIV is through the use of antiviral medication, such as HAART. But studies have shown that not everyone has the same positive effect when these drugs are administered. By understanding the virus and its pathogenesis, researchers will be able to develop new targets for therapeutic interventions. The public health significance of this project is to provide the valuable research that will lead towards such viable HIV-1 therapeutic interventions