Open AccessScreening for gene expression fluctuations reveals latency-promoting agents of HIV
Author(s) -
Yongde Lu,
Kathrin Bohn-Wippert,
Patrick J. Pazerunas,
Jennifer M. Moy,
Harpal Singh,
Roy D. Dar
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2012191118
Subject(s) - jurkat cells , biology , virus latency , gene silencing , gene expression , cell growth , microbiology and biotechnology , cell , cell culture , gene , immunology , genetics , t cell , viral replication , immune system
Significance Strategies to stabilize and suppress the latent cell reservoir of HIV have been proposed and need to be carefully examined. We demonstrate the use of time-lapse fluorescence microscopy to quantify HIV gene-expression dynamics and detect several latency-promoting agents (LPAs) that would be overlooked when screening for mean gene expression alone. These LPAs are structurally and functionally related to inhibitors of the thioredoxin/thioredoxin reductase redox pathway, which has been suggested as a promising HIV target. Some LPAs are Food and Drug Administration–approved and commercially available and can expand the currently limited LPA repertoire. This study provides a foundation to research suppression mechanisms of HIV gene expression, alternative latency-promoting therapies, and ultimately remove the need for antiretroviral therapy in patients.