Presenter: Brandon Lopez
Authors: J Lopez, Antonio Solis-Leal, Dalton Karlinsey, Jacob Fairholm
Faculty Advisor: Bradford Berges
Institution: Brigham Young University
Acquired immunodeficiency syndrome, known as AIDS, occurs when HIV depletes the CD4+ helper T cells of a patient below a functional threshold. The rate at which AIDS develops from the initial infection varies between patients. Patients may show Long-Term Non-Progressor (LTNP) and Rapid Progressor (RP) phenotypes, yet circumstances that cause the change in kinetics are not well understood. Mutations in the Viral Protein R (Vpr) gene have been linked to the changing kinetics in patients. Vpr is an accessory protein that affects cellular activities such as cell cycle progression and apoptosis. The R36W and R77Q mutants of this protein have been associated with RP and LTNP phenotypes, respectively; however, these conclusions are still controversial. We examined the effects that these Vpr mutations have in the context of an HIV-1 infection in the HuT78 T cell line. In our study, we found that R36W showed an increase in replication and cytotoxicity. We also found that the R77Q mutation resulted in an enhancement of apoptosis and G2 cell cycle arrest which was not seen in the WT, R36W, or Vpr null viruses. We showed the effects that the R77Q and the R36W mutations have in vitrothat may help explain what happens in an LTNP and RP infection. Currently, we are working to examine which cytokines are produced in vitro after infection of HuT78 cells. Next, we will examine these mutants in vivo in a humanized mice model to study the differing rates of AIDS progression.