A transient heritable memory regulates HIV reactivation from latency

Yiyang Lu, Harpal Singh, Abhyudai Singh, Roy D. Dar

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number102291
JournaliScience
Volume24
Issue number4
DOIs
StatePublished - Apr 23 2021

Keywords

  • Computational Molecular Modeling
  • Virology

ASJC Scopus subject areas

  • General

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