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Regulation of Mycobacterium tuberculosis-dependent HIV-1 transcription reveals a new role for NFAT5 in the toll-like receptor pathway.
- Source :
- PLoS Pathogens, Vol 8, Iss 4, p e1002620 (2012)
- Publication Year :
- 2012
- Publisher :
- Public Library of Science (PLoS), 2012.
-
Abstract
- Tuberculosis (TB) disease in HIV co-infected patients contributes to increased mortality by activating innate and adaptive immune signaling cascades that stimulate HIV-1 replication, leading to an increase in viral load. Here, we demonstrate that silencing of the expression of the transcription factor nuclear factor of activated T cells 5 (NFAT5) by RNA interference (RNAi) inhibits Mycobacterium tuberculosis (MTb)-stimulated HIV-1 replication in co-infected macrophages. We show that NFAT5 gene and protein expression are strongly induced by MTb, which is a Toll-like receptor (TLR) ligand, and that an intact NFAT5 binding site in the viral promoter of R5-tropic HIV-1 subtype B and subtype C molecular clones is required for efficent induction of HIV-1 replication by MTb. Furthermore, silencing by RNAi of key components of the TLR pathway in human monocytes, including the downstream signaling molecules MyD88, IRAK1, and TRAF6, significantly inhibits MTb-induced NFAT5 gene expression. Thus, the innate immune response to MTb infection induces NFAT5 gene and protein expression, and NFAT5 plays a crucial role in MTb regulation of HIV-1 replication via a direct interaction with the viral promoter. These findings also demonstrate a general role for NFAT5 in TLR- and MTb-mediated control of gene expression.
- Subjects :
- Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
Subjects
Details
- Language :
- English
- ISSN :
- 15537366 and 15537374
- Volume :
- 8
- Issue :
- 4
- Database :
- Directory of Open Access Journals
- Journal :
- PLoS Pathogens
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.f612b03154a48c98c12e86479dec68c
- Document Type :
- article
- Full Text :
- https://doi.org/10.1371/journal.ppat.1002620