Characterization of memory cytotoxic t lymphocyte responses in chronic hiv-1 infected individuals

Abstract

The three stages of untreated human immune deficiency virus type 1 (HIV-1) infection are acute HIV infection, chronic HIV infection, and acquired immunodeficiency syndrome (AIDS). Combination antiretroviral therapy (cART) is effective in treating chronic HIV infection but fails to completely clear the virus. Mutations in HIV epitopes recognized by cytotoxic T lymphocytes (CTL) could be a major contributing factor because they result in T cell mediated immune responses with limited effectiveness. In the absence of cART, it is the viral evolution within an individual during the course of infection under the pressure of host immune response that allows the virus to persist. To better understand viral pathogenesis and develop an effective HIV treatment, it is important to identify and characterize the evolution of mutations occurring within HIV CTL epitopes. Here I mapped the evolution of HIV CTL epitopes in chronically infected HIV-1 donors. Specifically, I fist 1) identified memory HIV CTL epitopes to HIV gag antigens p17/p24 from contemporaneous viral isolates obtained from long term HIV infected individuals and then 2) compared CTL responses to epitope sequences from the early stages of infection versus sequences after over 10 years of treatment and viral evolution. Using MHC class-1 binding predictive algorithm, the viral mutation was found to exhibit an unexpected pattern, that the reservoir variants has a higher binding affinity than its founder variant. Making use of an IFN- ELISpot Assay, the fact that the MHC class-1 binding affinity does not equal to the actual elicited CTL response has been noticed. Overall, this study has a significance in public health as it provided important information on the ability of HIV to escape CD8+ T lymphocyte detection and potentially contribute to the cure of the disease