dc.contributor.author | Ranjbar, Shahin | |
dc.contributor.author | Jasenosky, Luke D. | |
dc.contributor.author | Chow, Nancy Ann-Marie | |
dc.contributor.author | Goldfeld, Anne Esther | |
dc.date.accessioned | 2013-02-26T15:58:03Z | |
dc.date.issued | 2012 | |
dc.identifier.citation | Ranjbar, Shahin, Luke D. Jasenosky, Nancy Chow, and Anne E. Goldfeld. 2012. Regulation of Mycobacterium tuberculosis-dependent HIV-1 transcription reveals a new role for NFAT5 in the toll-like receptor pathway. PLoS Pathogens 8(4): e1002620. | en_US |
dc.identifier.issn | 1553-7366 | en_US |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:10345109 | |
dc.description.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. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Public Library of Science | en_US |
dc.relation.isversionof | doi:10.1371/journal.ppat.1002620 | en_US |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3320587/pdf/ | en_US |
dash.license | LAA | |
dc.subject | Biology | en_US |
dc.subject | Microbiology | en_US |
dc.subject | Medicine | en_US |
dc.subject | Infectious Diseases | en_US |
dc.subject | Bacterial Diseases | en_US |
dc.subject | Viral Diseases | en_US |
dc.title | Regulation of Mycobacterium tuberculosis-Dependent HIV-1 Transcription Reveals a New Role for NFAT5 in the Toll-Like Receptor Pathway | en_US |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en_US |
dc.relation.journal | PLoS Pathogens | en_US |
dash.depositing.author | Goldfeld, Anne Esther | |
dc.date.available | 2013-02-26T15:58:03Z | |
dc.identifier.doi | 10.1371/journal.ppat.1002620 | * |
dash.contributor.affiliated | Ranjbar, Shahin | |
dash.contributor.affiliated | Chow, Nancy Ann-Marie | |
dash.contributor.affiliated | Goldfeld, Anne | |