2025

What is the title of your project and what is it focused on?

The title of my project is “Molecular mechanisms of Vif adaptation to the active allele of A3H in humans”. APOBEC3H (A3H) is highly polymorphic in humans, with natural variants differing in both protein stability and antiviral activity. Individuals carrying an active A3H allele exhibit greater resistance to HIV-1 infection compared to those with an inactive allele. This project aims to investigate how HIV-1 Vif has evolved to counteract the active A3H allele, enabling viral replication and infection in these individuals.

How does your project align with the Center’s objectives?

This project aligns closely with the Center’s objective of understanding the evolution of Vif–APOBEC3 interactions. By applying cutting-edge structural determination methods and systematic biochemical approaches, I will investigate the molecular “arms race” between A3H and HIV-1 Vif. The goal of this research is to advance our understanding of Vif–A3H interactions, directly supporting the Center’s mission to elucidate how HIV accessory and regulatory proteins engage with host cellular systems.

What is the most inspiring aspect about your project/research focus?

The most inspiring aspect of my project is the use of HIV-1 Vif variants isolated from individuals who carry the active A3H allele, provided by our collaborator. Notably, the active A3H allele has been lost in the majority of the human population due to adaptive evolution. Despite its significance, the adaptation of HIV-1 Vif to the active A3H allele remains relatively understudied. In this research, I will employ structural, biochemical, and virological approaches to investigate the interaction between A3H and HIV-1 Vif. Uncovering the molecular mechanisms of Vif adaptation will provide critical insights into HIV-1 evolution and viral fitness.

What are your thoughts on the importance of continuing to build our understanding of HIV-host protein complexes and expanding therapeutic targets and treatment modalities for HIV/AIDS?

The evolutionary arms race between HIV-1 Vif and the A3H restriction factor plays a critical role in AIDS progression. HIV-1 variants with Vif proteins adapted to counteract active A3H pose a greater threat to individuals carrying this protective allele. Disrupting the interaction between Vif and A3H could restore the antiviral activity of A3H, unleashing its full restriction potential. This research has the potential to uncover strategies for targeting Vif, thereby restoring innate immune defenses against HIV-1 and related lentiviruses.