Analysis of the effect of drug resistance mutations within HIV-1 Pol epitopes on HLA-A*02-epitope binding and CD8+ T cell response

Faculty Development Competitive Research Grants Program 2025-2027

The HIV-1 pol gene encodes essential enzymes crucial for the HIV-1 life cycle. Consequently, Pol is a target for several antiretrovirals (ARV). Pol also stands out as one of the most immunogenic proteins, containing over 350 different Cytotoxic T lymphocytes (CTL/CD8) epitopes, including 84 well-characterized epitopes. ARVs can exert selection pressure on pol, amplifying drug-resistance mutations (DRMs). The DRM can significantly affect ART efficacy. Additionally, several DRMs emerge within or in the flanking region of the epitopes, which may also affect the epitope-HLA binding and T-cell response against the epitopes.

In this project, we aim to investigate the impact of DRMs in HIV-1 Pol epitopes on HLA-A*02-epitope binding and CD8+ T cell response. By analyzing the interactions between these mutations and HLA-A*02-epitopes, we aim to understand how drug resistance affects the ability of CD8+ T cells to recognize and target HIV-infected cells.

This research has the potential to provide valuable insights into the development of strategies to overcome drug resistance and enhance CD8+ T cell responses in HIV-infected individuals. Our findings could contribute to the design of more effective therapies for HIV and improve our understanding of immune responses against the virus.