Unknown

Dataset Information

0

A transient heritable memory regulates HIV reactivation from latency.


ABSTRACT: Reactivation of human immunodeficiency virus 1 (HIV-1) from latently infected T cells is a critical barrier to cure patients. It remains unknown whether reactivation of individual latent cells occurs stochastically in response to latency reversal agents (LRAs) or is a deterministic outcome of an underlying cell state. To characterize these single-cell responses, we leverage the classical Luria-Delbrück fluctuation test where single cells are isolated from a clonal population and exposed to LRAs after colony expansion. Data show considerable colony-to-colony fluctuations with the fraction of reactivating cells following a skewed distribution. Modeling systematic measurements of fluctuations over time uncovers a transient heritable memory that regulates HIV-1 reactivation, where single cells are in an LRA-responsive state for a few weeks before switching back to an irresponsive state. These results have enormous implications for designing therapies to purge the latent reservoir and further utilize fluctuation-based assays to uncover hidden transient cellular states underlying phenotypic heterogeneity.

SUBMITTER: Lu Y 

PROVIDER: S-EPMC8050369 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC2614643 | biostudies-literature
| S-EPMC2722084 | biostudies-literature
2010-06-06 | E-GEOD-1441 | biostudies-arrayexpress
| S-EPMC2876650 | biostudies-literature
| S-EPMC3992654 | biostudies-literature
| S-EPMC6172763 | biostudies-literature
2004-08-16 | GSE1441 | GEO
| S-EPMC4495168 | biostudies-literature
| S-EPMC10537590 | biostudies-literature
| S-EPMC5573388 | biostudies-literature