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HIV-1-mediated insertional activation of STAT5B and BACH2 trigger viral reservoir in T regulatory cells

Authors :
Cesana, D
Santoni De Sio, F
Rudilosso, L
Gallina, P
Calabria, A
Beretta, S
Merelli, I
Bruzzesi, E
Passerini, L
Nozza, S
Vicenzi, E
Poli, G
Gregori, S
Tambussi, G
Montini, E
Montini, E.
CALABRIA, ANDREA
BERETTA, STEFANO
MERELLI, IVAN
PASSERINI, LAURA
Cesana, D
Santoni De Sio, F
Rudilosso, L
Gallina, P
Calabria, A
Beretta, S
Merelli, I
Bruzzesi, E
Passerini, L
Nozza, S
Vicenzi, E
Poli, G
Gregori, S
Tambussi, G
Montini, E
Montini, E.
CALABRIA, ANDREA
BERETTA, STEFANO
MERELLI, IVAN
PASSERINI, LAURA
Publication Year :
2017

Abstract

HIV-1 insertions targeting BACH2 or MLK2 are enriched and persist for decades in hematopoietic cells from patients under combination antiretroviral therapy. However, it is unclear how these insertions provide such selective advantage to infected cell clones. Here, we show that in 30/87 (34%) patients under combination antiretroviral therapy, BACH2, and STAT5B are activated by insertions triggering the formation of mRNAs that contain viral sequences fused by splicing to their first protein-coding exon. These chimeric mRNAs, predicted to express full-length proteins, are enriched in T regulatory and T central memory cells, but not in other T lymphocyte subsets or monocytes. Overexpression of BACH2 or STAT5B in primary T regulatory cells increases their proliferation and survival without compromising their function. Hence, we provide evidence that HIV-1-mediated insertional activation of BACH2 and STAT5B favor the persistence of a viral reservoir in T regulatory cells in patients under combination antiretroviral therapy.

Details

Database :
OAIster
Notes :
English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1308922469
Document Type :
Electronic Resource