Use of bioinformatics tools to assess Abundance and Sequence Variation of HIV-1 LTR U3 Transcription Factor Binding Sites and their Association with HIV-1 LVR Reactivation

HIV-1 persists in people on antiretroviral therapy (ART) because the virus can hide in long-lived immune cells, forming a latent reservoir. These hidden viruses can reactivate if treatment stops, making HIV difficult to cure. Efforts to reverse latency aim to “wake up” these silent viruses so the immune system or drugs can eliminate them, but only a fraction of proviruses respond to stimulation. The reasons for this variability are not fully understood, particularly for the main HIV subtypes circulating in Uganda (A1, D, and their recombinants).

This project investigates how the abundance and sequence variation of key transcription factor binding sites in the U3 region of the HIV genome influence viral transcription and reactivation. Using advanced sequencing and bioinformatics, the research will analyze proviral sequences from the Rakai HIV Reservoir Cohort to identify patterns associated with stronger or weaker reactivation. By linking viral DNA features to measures of latent virus activity, the study aims to explain why some proviruses resist reactivation, providing insights that could guide future HIV cure strategies.

Faculty Supervisor:

Stephen Barr;Jessica Prodger

Student:

Partner:

Makerere University

Discipline:

Life Sciences

Sector:

Health and Related Sciences and Technology; Biotechnology

University:

The University of Western Ontario

Program: