Open AccessHuman splice factors contribute to latent HIV infection in primary cell models and blood CD4+ T cells from ART-treated individuals
Author(s) -
Sara Morón-López,
Sushama Telwatte,
Indra Sarabia,
Emilie Battivelli,
Mauricio Montaño,
Amanda B. Macedo,
Dvir Aran,
Atul J. Butte,
R. Brad Jones,
Alberto Bosque,
Eric Verdin,
Warner C. Greene,
Joseph K. Wong,
Steven A. Yukl
Publication year - 2020
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009060
Subject(s) - human immunodeficiency virus (hiv) , splice , immunology , virology , biology , medicine , genetics , gene
It is unclear what mechanisms govern latent HIV infection in vivo or in primary cell models. To investigate these questions, we compared the HIV and cellular transcription profile in three primary cell models and peripheral CD4 + T cells from HIV-infected ART-suppressed individuals using RT-ddPCR and RNA-seq. All primary cell models recapitulated the block to HIV multiple splicing seen in cells from ART-suppressed individuals, suggesting that this may be a key feature of HIV latency in primary CD4 + T cells. Blocks to HIV transcriptional initiation and elongation were observed more variably among models. A common set of 234 cellular genes, including members of the minor spliceosome pathway, was differentially expressed between unstimulated and activated cells from primary cell models and ART-suppressed individuals, suggesting these genes may play a role in the blocks to HIV transcription and splicing underlying latent infection. These genes may represent new targets for therapies designed to reactivate or silence latently-infected cells.