Dynamic antigen expression and cytotoxic T cell resistance in HIV reservoir clones - PubMed
4 hours ago
- #HIV reservoir
- #immune-based cure
- #CTL resistance
- Clonally expanded CD4+ T-cells with rebound-competent HIV persist lifelong during ART.
- Latency is a major barrier to HIV eradication, resistant to pharmacological reversal.
- Sustained immune pressure can erode HIV reservoirs over time.
- Authentic reservoir clones (ARCs) proliferate and accumulate while producing infectious virus without succumbing to cytopathicity.
- Only small fractions of ARCs express HIV proteins at any given time, linked to conserved host transcriptional programs.
- ARCs are refractory to potent T-cell stimulation but show vulnerability to sustained CD8+ cytotoxic T-lymphocyte (CTL) pressure.
- Ex vivo CD8+ T-cell responses are poorly cytotoxic, and in vivo erosion of ARCs is slow.
- A regulatory T-cell ARC showed intrinsic resistance to CTL, linked to low oxidative stress, reversible with deferoxamine.
- Findings highlight intrinsic resistance pathways as therapeutic targets for immune-based HIV cure strategies.