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Title: Interleukin-7 induces HIV replication in primary naive T cells through a nuclear factor of activated T cell (NFAT)-dependent pathway

Abstract

Interleukin (IL)-7 plays several roles critical to T cell maturation, survival, and homeostasis. Because of these functions, IL-7 is under investigation as an immune-modulator for therapeutic use in lymphopenic clinical conditions, including HIV. We reported that naive T cells, typically not permissive to HIV, can be productively infected when pre-treated with IL-7. We evaluated the mechanism by which IL-7-mediates this effect. IL-7 potently up-regulated the transcriptional factor NFAT, but had no effect on NF{kappa}B. Blocking NFAT activity using a number of reagents, such as Cyclosporin A, FK-506, or the NFAT-specific inhibitor known as VIVIT peptide, all markedly reduced IL-7-mediated induction of HIV replication in naive T cells. Additional neutralization of cytokines present in IL-7-treated cultures and/or those that have NFAT-binding sequences within their promotors indicated that IL-10, IL-4, and most significantly IFN{gamma}, all contribute to IL-7-induction of HIV productive replication in naive T cells. These data clarify the mechanism by which IL-7 can overcome the block to HIV productive infection in naive T cells, despite their quiescent cell status. These findings are relevant to the treatment of HIV disease and understanding HIV pathogenesis in the naive CD4+ T cell compartment, especially in light of the vigorous pursuit of IL-7 asmore » an in vivo immune modulator.« less

Authors:
 [1];  [1];  [2]
  1. Department of Immunology/Microbiology, Rush University Medical Center, 1735 West Harrison Street, 614 Cohn, Chicago, IL 60612 (United States)
  2. Department of Immunology/Microbiology, Rush University Medical Center, 1735 West Harrison Street, 614 Cohn, Chicago, IL 60612 (United States). E-mail: lalharth@rush.edu
Publication Date:
OSTI Identifier:
20850529
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 350; Journal Issue: 2; Other Information: DOI: 10.1016/j.virol.2006.02.019; PII: S0042-6822(06)00110-3; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AIDS VIRUS; HOMEOSTASIS; IN VIVO; LYMPHOKINES; PATHOGENESIS; PEPTIDES; REAGENTS; THERAPEUTIC USES; VIRAL DISEASES

Citation Formats

Managlia, Elizabeth Z., Landay, Alan, and Al-Harthi, Lena. Interleukin-7 induces HIV replication in primary naive T cells through a nuclear factor of activated T cell (NFAT)-dependent pathway. United States: N. p., 2006. Web. doi:10.1016/j.virol.2006.02.019.
Managlia, Elizabeth Z., Landay, Alan, & Al-Harthi, Lena. Interleukin-7 induces HIV replication in primary naive T cells through a nuclear factor of activated T cell (NFAT)-dependent pathway. United States. doi:10.1016/j.virol.2006.02.019.
Managlia, Elizabeth Z., Landay, Alan, and Al-Harthi, Lena. Wed . "Interleukin-7 induces HIV replication in primary naive T cells through a nuclear factor of activated T cell (NFAT)-dependent pathway". United States. doi:10.1016/j.virol.2006.02.019.
@article{osti_20850529,
title = {Interleukin-7 induces HIV replication in primary naive T cells through a nuclear factor of activated T cell (NFAT)-dependent pathway},
author = {Managlia, Elizabeth Z. and Landay, Alan and Al-Harthi, Lena},
abstractNote = {Interleukin (IL)-7 plays several roles critical to T cell maturation, survival, and homeostasis. Because of these functions, IL-7 is under investigation as an immune-modulator for therapeutic use in lymphopenic clinical conditions, including HIV. We reported that naive T cells, typically not permissive to HIV, can be productively infected when pre-treated with IL-7. We evaluated the mechanism by which IL-7-mediates this effect. IL-7 potently up-regulated the transcriptional factor NFAT, but had no effect on NF{kappa}B. Blocking NFAT activity using a number of reagents, such as Cyclosporin A, FK-506, or the NFAT-specific inhibitor known as VIVIT peptide, all markedly reduced IL-7-mediated induction of HIV replication in naive T cells. Additional neutralization of cytokines present in IL-7-treated cultures and/or those that have NFAT-binding sequences within their promotors indicated that IL-10, IL-4, and most significantly IFN{gamma}, all contribute to IL-7-induction of HIV productive replication in naive T cells. These data clarify the mechanism by which IL-7 can overcome the block to HIV productive infection in naive T cells, despite their quiescent cell status. These findings are relevant to the treatment of HIV disease and understanding HIV pathogenesis in the naive CD4+ T cell compartment, especially in light of the vigorous pursuit of IL-7 as an in vivo immune modulator.},
doi = {10.1016/j.virol.2006.02.019},
journal = {Virology},
number = 2,
volume = 350,
place = {United States},
year = {Wed Jul 05 00:00:00 EDT 2006},
month = {Wed Jul 05 00:00:00 EDT 2006}
}