Poster #83 - April Boyd

Evolution of the HIV Envelope Protein and Its Connection to HIV Reservoir Dynamics: Longitudinal Analysis Over 13 Years

April E. Boyd LaMont Cannon, Ph.D.

Evolution of the HIV Envelope Protein and Its Connection to HIV Reservoir Dynamics: Longitudinal Analysis Over 13 Years April E. Boyd1 and Dr. LaMont Cannon1 1School of Life Sciences and Sustainability, VCU Life Sciences Background: HIV-related mortality has significantly declined due to the use of combination antiretroviral therapies (ART), making an HIV diagnosis no longer a fatal outcome when properly treated and managed. However, discontinuing ART leads to viral resurgence, requiring lifelong adherence to treatment. Given the numerous challenges associated with long-term treatment adherence, finding a cure to eliminate the persistent viral load in infected individuals remains a critical priority, emphasizing the importance of HIV eradication. A major obstacle to achieving HIV eradication is the persistence of cells harboring replication-competent HIV, collectively known as the HIV reservoir. Research on the HIV reservoir reveals that the composition of proviruses changes dynamically during ART. The HIV envelope glycoprotein binds to CD4 cell receptors to mediate viral entry. The envelope protein's variable loop regions are key contributors to these processes. In this study, we aim to investigate the envelope protein to further define its conformational changes over time. Methods: We created a bioinformatic pipeline that automatically analyzes temporal HIV amino acid sequence data to detect, quantify and predict structural changes in HIV proteins over time. Results: Our analysis revealed multiple alterations in variable loop regions of the env protein including insertions, deletions, and missense modifications throughout the dataset. RMS distance analysis revealed structural shifts in 3 of the 5 variable loops that correspond with reservoir dynamics in the early-to-late temporal changes. Conclusion: This long-term, multi-subject analysis provides a unique opportunity to track measurable compositional changes over time, addressing critical gaps in our understanding of HIV persistence.