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BACH2 Controls Seeding and Establishment of Long-Lived HIV-1 Reservoir in CD4+ T cells

GSE275936 Homo sapiens Expression profiling by high throughput sequencing 8 samples Submitted 2024/11/01 Platform GPL11154
Summary
Despite antiretroviral therapy, HIV mainly persists in memory CD4+ T cells in people living with HIV. Most long-lived viral reservoir cells are infected near the time of therapy initiation. A better understanding of the early events in reservoir seeding presents opportunities for preventing latent reservoir formation. Here, we demonstrated that CD4+ T cells expressing CCR5, permissive to HIV-1 infection, are effector or terminally differentiated cells. BACH2 is expressed by a small subset of CCR5+ cells and reverses their terminal differentiation. BACH2-mediated memory differentiation is impeded due to heightened inflammation before treatment initiation. Mice with a BACH2 knockout human immune system has a reduced frequency of HIV-1 reservoir cells and do not experience virus rebound after treatment discontinuation. Our study reveals that BACH2 is essential to the seeding of long-lived HIV-1 reservoir and demonstrates the potential of targeting BACH2 at the time of treatment initiation to eliminate HIV-1 reservoirs in T cells.
Published in
BACH2 promotes seeding and establishment of long-lived HIV-1 reservoir in memory CD4(+) T cells
Gao H, Li Y, Tiwari R et al. · Cell reports. Medicine 2025 · PMID 40845840 · doi:10.1016/j.xcrm.2025.102311
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Also filed as BioProject PRJNA1153621 and SRA study SRP529262. Searching any of these in the dataset finder brings you back here.

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