Loss of RORγt DNA Binding Activity Inhibits IL-17 Expression in HIV-1 Infected Indian Individuals

2013 ◽  
Vol 26 (1) ◽  
pp. 60-67 ◽  
Author(s):  
Alpana Singh ◽  
Madhu Vajpayee ◽  
Sharique A. Ali ◽  
Neeraj Kumar Chauhan
2016 ◽  
Vol 71 (8) ◽  
pp. 2083-2088 ◽  
Author(s):  
Kaitlin Anstett ◽  
Vincent Cutillas ◽  
Robert Fusco ◽  
Thibault Mesplède ◽  
Mark A. Wainberg

1995 ◽  
Vol 217 (3) ◽  
pp. 802-810 ◽  
Author(s):  
I.R. Haugan ◽  
B.M. Nilsen ◽  
S. Worland ◽  
L. Olsen ◽  
D.E. Helland

1992 ◽  
Vol 8 (2) ◽  
pp. 297-304 ◽  
Author(s):  
AMY M. WOERNER ◽  
MICHAEL KLUTCH ◽  
JUDITH G. LEVIN ◽  
CAROL J. MARCUS-SEKURA

1997 ◽  
Vol 110 (22) ◽  
pp. 2883-2893
Author(s):  
F. Bachelerie ◽  
M.S. Rodriguez ◽  
C. Dargemont ◽  
D. Rousset ◽  
D. Thomas ◽  
...  

De novo synthesized IkappaBalpha accumulates transiently in the nucleus where it inhibits NF-kappaB-dependent transcription and reduces nuclear NF-kappaB content. A sequence present in the C-terminal domain of IkappaBalpha and homologous to the HIV-1 Rev nuclear export signal (NES) has been recently defined as a functional NES conferring on IkappaBalpha the ability to export IkappaBalpha/NF-kappaB complexes. Rev utilises its RNA-binding activity and NES sequence to promote specifically the transport of unspliced and monospliced viral RNAs to the cytoplasm. The object of this work was to determine if nuclear IkappaBalpha could interfere with Rev-dependent transport of viral RNA from the nucleus to the cytoplasm. We report that accumulation of IkappaBalpha in the cell nucleus blocks viral replication. This effect could be dissociated from the capacity of IkappaBalpha to inhibit NF-kappaB-DNA-binding activity and required a functional IkappaBalpha NES motif. Indeed, mutation of the NES abrogated the capacity of IkappaBalpha to inhibit Rev-dependent mechanisms involved in the replication of either wild-type or NF-kappaB-mutated HIV-1 molecular clones. Nuclear accumulation of a reporter protein tagged with a nuclear localization signal (NLS) and fused to the IkappaBalpha NES motif (NLS-PK-NES) was sufficient to inhibit HIV-1 replication at a post-transcriptional level by specifically blocking the expression of a Rev-dependent gene. Furthermore, in cells pulsed with TNF, a treatment which favors nuclear accumulation of newly synthesized IkappaBalpha, NLS-PK-NES expression promoted sustained accumulation of nuclear NF-kappaB lacking DNA-binding activity. This NES-mediated accumulation of inactive nuclear NF-kappaB is likely the consequence of interference in the IkappaBalpha-mediated export of NF-kappaB. These findings indicate that IkappaBalpha and Rev compete for the same nuclear export pathway and suggest that nuclear accumulation of IkappaBalpha, which would occur during normal physiological cell activation process, may interfere with the Rev-NES-mediated export pathway of viral RNAs, thus inhibiting HIV-1 replication.


2003 ◽  
Vol 71 (4) ◽  
pp. 2058-2064 ◽  
Author(s):  
Rany Condos ◽  
Bindu Raju ◽  
Antony Canova ◽  
Ben-Yang Zhao ◽  
Michael Weiden ◽  
...  

ABSTRACT Tuberculosis is the seventh leading cause of morbidity and mortality in the world, with eight million cases per year. Animal and human studies demonstrate an enrichment of CD4 cells at sites of disease, with a more favorable clinical course when there is a Th1 response with the presence of gamma interferon (IFN-γ). We previously treated patients who had multidrug-resistant tuberculosis with recombinant IFN-γ (rIFN-γ) in aerosol form and were able to convert smear-positive cases to smear negative with 12 treatments over 1 month. We hypothesized that rIFN-γ would induce signal transducer and activator of transcription (STAT) and interferon regulatory factor (IRF) binding activity in alveolar macrophages (AM). AM treated in vitro showed clear upregulation of STAT-1 and IRF-1 by rIFN-γ. STAT-1 was not activated and IRF-1 was only weakly induced after 1 day of infection by Mycobacterium tuberculosis TN913. In bronchoalveolar lavage (BAL) cells obtained from 10 of 10 tuberculosis patients 10 ± 2 days post-antituberculosis treatment, there was no detectable STAT-1 or IRF-1 DNA-binding activity. After 4 weeks of treatment with rIFN-γ aerosol in addition to the antituberculosis drugs, 10 of 10 patients had increased STAT-1, IRF-1, and/or IRF-9 DNA-binding activity in BAL cells from lung segments shown radiographically to be involved and in those shown to be uninvolved. Symptoms and chest radiographs improved, and amounts of macrophage inflammatory cytokines and human immunodeficiency virus type 1 (HIV-1) viral loads (in five of five HIV-1-coinfected patients) declined in the second BAL specimens. rIFN-γ aerosol induces signal transduction and gene expression in BAL cells and should be evaluated for efficacy in a randomized, controlled clinical trial.


Virology ◽  
1993 ◽  
Vol 194 (1) ◽  
pp. 338-344 ◽  
Author(s):  
Thomas M.J. Niederman ◽  
W.Randall Hastings ◽  
Sylvie Luria ◽  
Juan C. Bandres ◽  
Lee Ratner

1997 ◽  
Vol 61 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Hans S. L. M. Nottet ◽  
Inge I. M. D. Moelans ◽  
N. Machiel de Vos ◽  
Loek de Graaf ◽  
Maarten R. Visser ◽  
...  

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