Crossref journal-article
Oxford University Press (OUP)
The Journal of Immunology (286)
Abstract

AbstractVirus infection of host cells activates a set of cellular genes, including cytokines, IFNs, and chemokines, involved in antiviral defense and immune activation. Previous studies demonstrated that virus-induced transcriptional activation of a member of the human CC-chemokine RANTES required activation of the latent transcription factors IFN-regulatory factor (IRF)-3 and NF-κB via posttranslational phosphorylation. In the present study, we further characterized the regulatory control of RANTES transcription during virus infection using in vivo genomic footprinting analyses. IRF-3, the related IRF-7, and NF-κB are identified as important in vivo binding factors required for the cooperative induction of RANTES transcription after virus infection. Using fibroblastic or myeloid cells, we demonstrate that the kinetics and strength of RANTES virus-induced transcription are highly dependent on the preexistence of IRFs and NF-κB. Use of dominant negative mutants of either IκB-α or IRF-3 demonstrate that disruption of either pathway dramatically abolishes the ability of the other to bind and activate RANTES expression. Furthermore, coexpression of IRF-3, IRF-7, and p65/p50 leads to synergistic activation of RANTES promoter transcription. These studies reveal a model of virus-mediated RANTES promoter activation that involves cooperative synergism between IRF-3/IRF-7 and NF-κB factors.

Bibliography

Génin, P., Algarté, M., Roof, P., Lin, R., & Hiscott, J. (2000). Regulation of RANTES Chemokine Gene Expression Requires Cooperativity Between NF-κB and IFN-Regulatory Factor Transcription Factors. The Journal of Immunology, 164(10), 5352–5361.

Authors 5
  1. Pierre Génin (first)
  2. Michèle Algarté (additional)
  3. Philippe Roof (additional)
  4. Rongtuan Lin (additional)
  5. John Hiscott (additional)
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Dates
Type When
Created 11 years, 4 months ago (April 21, 2014, 10:30 p.m.)
Deposited 7 months, 3 weeks ago (Jan. 2, 2025, 12:23 p.m.)
Indexed 3 weeks, 1 day ago (Aug. 2, 2025, 12:08 a.m.)
Issued 25 years, 3 months ago (May 15, 2000)
Published 25 years, 3 months ago (May 15, 2000)
Published Print 25 years, 3 months ago (May 15, 2000)
Funders 0

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@article{Ge_nin_2000, title={Regulation of RANTES Chemokine Gene Expression Requires Cooperativity Between NF-κB and IFN-Regulatory Factor Transcription Factors}, volume={164}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.164.10.5352}, DOI={10.4049/jimmunol.164.10.5352}, number={10}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Génin, Pierre and Algarté, Michèle and Roof, Philippe and Lin, Rongtuan and Hiscott, John}, year={2000}, month=may, pages={5352–5361} }