• Subjects Adaptive immunity Virology Abstract Clonally expanded CD4+T-cells harboring rebound-competent HIV persist lifelong during ART1-5. • Latency is considered the principal barrier to viral eradication and has resisted pharmacological reversal6,7, yet sustained immune pressure appears to erode reservoirs8-15. • Recent advances have yielded glimpses into exceptionally rare reservoir-harboring cells, implicating pro-survival properties in persistence16-18. • Here, we isolate and characterize authentic reservoir clones (ARCs) that robustly proliferate and accumulate while producing infectious virus, without overtly succumbing to cytopathicity. • At any moment, only small fractions of ARCs expressed HIV proteins, a state associated with conserved host transcriptional programs but remarkably refractory to potent T-cell stimulation. • Nevertheless, sustained co-culture with a CD8+cytotoxic T-lymphocyte clone substantially culled proliferating ARCs, revealing time-integrated vulnerability to immune pressure.

Article Summaries:

  • Abstract Clonally expanded CD4+ T-cells harboring rebound-competent HIV persist lifelong during ART1-5. Latency is considered the principal barrier to viral eradication and has resisted pharmacological reversal6,7, yet sustained immune pressure appears to erode reservoirs8-15. Recent advances have yielded glimpses into exceptionally rare reservoir-harboring cells, implicating pro-survival properties in persistence16-18. Here, we isolate and characterize authentic reservoir clones (ARCs) that robustly proliferate and accumulate while producing infectious virus, without overtly succumbing to cyt

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