The Evolving HIV-1 Proviral Landscape: Integration Site Dynamics and Biases Under Drug Resistance and Viral Latency
Year: 2025
Type: article
Abstract: Human immunodeficiency virus type 1 (HIV-1) establishes lifelong infection by integrating its genome into host DNA. While integrase strand transfer inhibitors (INSTIs) effectively block new integration events, therapeutic- and immune-mediated clearance are limited by two challenges: the emergence of drug-resistant variants and the persistence of latent reservoirs. As integration underlies both INSTI resistance and latency, this thesis uses a bioinformatics approach to investigate factors shaping HIV-1 integration site dynamics. Under prolonged drug exposure, we showed that proviral landscapes shift towards genomic regions that support long-term persistence, driven in part by drug-resistant variants harbouring major mutations (e.g., R263K in HIV-1 integrase). We also identified host proteins (e.g., nucleophosmin) that interact with HIV-1 pre-integration complexes, some of which direct integration toward G-quadruplex-rich regions—structures linked to both latent and reactivated proviral states. Altogether, our work offers key insights into how integration shapes drug resistance and latency, guiding future strategies against persistent infections.
Author: Barua, Emile
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7037925126
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