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Characterization of two candidate genes, NCoA3 and IRF8, potentially involved in the control of HIV-1 latency

BACKGROUND: The persistence of latent HIV-1 reservoirs is the principal barrier preventing the eradication of HIV-1 infection in patients by current antiretroviral therapy. It is thus crucial to understand the molecular mechanisms involved in the establishment, maintenance and reactivation of HIV-1...

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Autores principales: Munier, Sandie, Delcroix-Genête, Delphine, Carthagéna, Laëtitia, Gumez, Audrey, Hazan, Uriel
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1310520/
https://www.ncbi.nlm.nih.gov/pubmed/16305739
http://dx.doi.org/10.1186/1742-4690-2-73
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author Munier, Sandie
Delcroix-Genête, Delphine
Carthagéna, Laëtitia
Gumez, Audrey
Hazan, Uriel
author_facet Munier, Sandie
Delcroix-Genête, Delphine
Carthagéna, Laëtitia
Gumez, Audrey
Hazan, Uriel
author_sort Munier, Sandie
collection PubMed
description BACKGROUND: The persistence of latent HIV-1 reservoirs is the principal barrier preventing the eradication of HIV-1 infection in patients by current antiretroviral therapy. It is thus crucial to understand the molecular mechanisms involved in the establishment, maintenance and reactivation of HIV-1 latency. Since chromatin remodeling has been implicated in the transcriptional reactivation of the HIV-1 promoter, we assessed the role of the histone deacetylase inhibitor sodium butyrate (NaB) on two HIV-1 latently infected cell lines (U1 and ACH-2) gene expression. RESULTS: Analysis of microarrays data led us to select two candidate genes: NCoA3 (Nuclear Receptor Coactivator 3), a nuclear receptor coactivator and IRF8 (Interferon Regulatory Factor 8), an interferon regulatory factor. NCoA3 gene expression is upregulated following NaB treatment of latently infected cells whereas IRF8 gene expression is strongly downregulated in the promonocytic cell line following NaB treatment. Their differential expressions were confirmed at the transcriptional and translational levels. Moreover, NCoA3 gene expression was also upregulated after treatment of U1 and ACH-2 cells with phorbol myristyl acetate (PMA) but not trichostatin A (TSA) and after treatment with NaB of two others HIV-1 latently infected cell lines (OM10.1 and J1.1). IRF8 gene is only expressed in U1 cells and was also downregulated after treatment with PMA or TSA. Functional analyses confirmed that NCoA3 synergizes with Tat to enhance HIV-1 promoter transcription and that IRF8 represses the IRF1-mediated activation through the HIV-1 promoter Interferon-stimulated response element (ISRE). CONCLUSION: These results led us to postulate that NCoA3 could be involved in the transcriptional reactivation of the HIV-1 promoter from latency and that IRF8 may contribute to the maintenance of the latent state in the promonocytic cell line. Implication of these factors in the maintenance or reactivation of the viral latency may provide potential new targets to control HIV-1 replication in latent viral reservoirs.
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spelling pubmed-13105202005-12-10 Characterization of two candidate genes, NCoA3 and IRF8, potentially involved in the control of HIV-1 latency Munier, Sandie Delcroix-Genête, Delphine Carthagéna, Laëtitia Gumez, Audrey Hazan, Uriel Retrovirology Research BACKGROUND: The persistence of latent HIV-1 reservoirs is the principal barrier preventing the eradication of HIV-1 infection in patients by current antiretroviral therapy. It is thus crucial to understand the molecular mechanisms involved in the establishment, maintenance and reactivation of HIV-1 latency. Since chromatin remodeling has been implicated in the transcriptional reactivation of the HIV-1 promoter, we assessed the role of the histone deacetylase inhibitor sodium butyrate (NaB) on two HIV-1 latently infected cell lines (U1 and ACH-2) gene expression. RESULTS: Analysis of microarrays data led us to select two candidate genes: NCoA3 (Nuclear Receptor Coactivator 3), a nuclear receptor coactivator and IRF8 (Interferon Regulatory Factor 8), an interferon regulatory factor. NCoA3 gene expression is upregulated following NaB treatment of latently infected cells whereas IRF8 gene expression is strongly downregulated in the promonocytic cell line following NaB treatment. Their differential expressions were confirmed at the transcriptional and translational levels. Moreover, NCoA3 gene expression was also upregulated after treatment of U1 and ACH-2 cells with phorbol myristyl acetate (PMA) but not trichostatin A (TSA) and after treatment with NaB of two others HIV-1 latently infected cell lines (OM10.1 and J1.1). IRF8 gene is only expressed in U1 cells and was also downregulated after treatment with PMA or TSA. Functional analyses confirmed that NCoA3 synergizes with Tat to enhance HIV-1 promoter transcription and that IRF8 represses the IRF1-mediated activation through the HIV-1 promoter Interferon-stimulated response element (ISRE). CONCLUSION: These results led us to postulate that NCoA3 could be involved in the transcriptional reactivation of the HIV-1 promoter from latency and that IRF8 may contribute to the maintenance of the latent state in the promonocytic cell line. Implication of these factors in the maintenance or reactivation of the viral latency may provide potential new targets to control HIV-1 replication in latent viral reservoirs. BioMed Central 2005-11-23 /pmc/articles/PMC1310520/ /pubmed/16305739 http://dx.doi.org/10.1186/1742-4690-2-73 Text en Copyright © 2005 Munier et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Munier, Sandie
Delcroix-Genête, Delphine
Carthagéna, Laëtitia
Gumez, Audrey
Hazan, Uriel
Characterization of two candidate genes, NCoA3 and IRF8, potentially involved in the control of HIV-1 latency
title Characterization of two candidate genes, NCoA3 and IRF8, potentially involved in the control of HIV-1 latency
title_full Characterization of two candidate genes, NCoA3 and IRF8, potentially involved in the control of HIV-1 latency
title_fullStr Characterization of two candidate genes, NCoA3 and IRF8, potentially involved in the control of HIV-1 latency
title_full_unstemmed Characterization of two candidate genes, NCoA3 and IRF8, potentially involved in the control of HIV-1 latency
title_short Characterization of two candidate genes, NCoA3 and IRF8, potentially involved in the control of HIV-1 latency
title_sort characterization of two candidate genes, ncoa3 and irf8, potentially involved in the control of hiv-1 latency
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1310520/
https://www.ncbi.nlm.nih.gov/pubmed/16305739
http://dx.doi.org/10.1186/1742-4690-2-73
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