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NFAT5 regulates HIV-1 in primary monocytes via a highly conserved long terminal repeat site.
- Source :
- PLoS Pathogens, Vol 2, Iss 12, p e130 (2006)
- Publication Year :
- 2006
- Publisher :
- Public Library of Science (PLoS), 2006.
-
Abstract
- To replicate, HIV-1 capitalizes on endogenous cellular activation pathways resulting in recruitment of key host transcription factors to its viral enhancer. RNA interference has been a powerful tool for blocking key checkpoints in HIV-1 entry into cells. Here we apply RNA interference to HIV-1 transcription in primary macrophages, a major reservoir of the virus, and specifically target the transcription factor NFAT5 (nuclear factor of activated T cells 5), which is the most evolutionarily divergent NFAT protein. By molecularly cloning and sequencing isolates from multiple viral subtypes, and performing DNase I footprinting, electrophoretic mobility shift, and promoter mutagenesis transfection assays, we demonstrate that NFAT5 functionally interacts with a specific enhancer binding site conserved in HIV-1, HIV-2, and multiple simian immunodeficiency viruses. Using small interfering RNA to ablate expression of endogenous NFAT5 protein, we show that the replication of three major HIV-1 viral subtypes (B, C, and E) is dependent upon NFAT5 in human primary differentiated macrophages. Our results define a novel host factor-viral enhancer interaction that reveals a new regulatory role for NFAT5 and defines a functional DNA motif conserved across HIV-1 subtypes and representative simian immunodeficiency viruses. Inhibition of the NFAT5-LTR interaction may thus present a novel therapeutic target to suppress HIV-1 replication and progression of AIDS.
- Subjects :
- Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
Subjects
Details
- Language :
- English
- ISSN :
- 15537366 and 15537374
- Volume :
- 2
- Issue :
- 12
- Database :
- Directory of Open Access Journals
- Journal :
- PLoS Pathogens
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.546433206d9f4883a0715ad8ab5140ea
- Document Type :
- article
- Full Text :
- https://doi.org/10.1371/journal.ppat.0020130