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The aryl hydrocarbon receptor and interferon gamma generate antiviral states via transcriptional repression

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor whose activation induces the expression of numerous genes, with many effects on cells. However, AhR activation is not known to affect the replication of viruses. We show that AhR activation in macrophages causes a block t...

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Autores principales: Kueck, Tonya, Cassella, Elena, Holler, Jessica, Kim, Baek, Bieniasz, Paul D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120754/
https://www.ncbi.nlm.nih.gov/pubmed/30132758
http://dx.doi.org/10.7554/eLife.38867
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author Kueck, Tonya
Cassella, Elena
Holler, Jessica
Kim, Baek
Bieniasz, Paul D
author_facet Kueck, Tonya
Cassella, Elena
Holler, Jessica
Kim, Baek
Bieniasz, Paul D
author_sort Kueck, Tonya
collection PubMed
description The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor whose activation induces the expression of numerous genes, with many effects on cells. However, AhR activation is not known to affect the replication of viruses. We show that AhR activation in macrophages causes a block to HIV-1 and HSV-1 replication. We find that AhR activation transcriptionally represses cyclin-dependent kinase (CDK)1/2 and their associated cyclins, thereby reducing SAMHD1 phosphorylation, cellular dNTP levels and both HIV-1 and HSV-1 replication. Remarkably, a different antiviral stimulus, interferon gamma (IFN-γ), that induces a largely non-overlapping set of genes, also transcriptionally represses CDK1, CDK2 and their associated cyclins, resulting in similar dNTP depletion and antiviral effects. Concordantly, the SIV Vpx protein provides complete and partial resistance to the antiviral effects of AhR and IFN-γ, respectively. Thus, distinct antiviral signaling pathways converge on CDK/cyclin repression, causing inhibition of viral DNA synthesis and replication.
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spelling pubmed-61207542018-09-06 The aryl hydrocarbon receptor and interferon gamma generate antiviral states via transcriptional repression Kueck, Tonya Cassella, Elena Holler, Jessica Kim, Baek Bieniasz, Paul D eLife Immunology and Inflammation The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor whose activation induces the expression of numerous genes, with many effects on cells. However, AhR activation is not known to affect the replication of viruses. We show that AhR activation in macrophages causes a block to HIV-1 and HSV-1 replication. We find that AhR activation transcriptionally represses cyclin-dependent kinase (CDK)1/2 and their associated cyclins, thereby reducing SAMHD1 phosphorylation, cellular dNTP levels and both HIV-1 and HSV-1 replication. Remarkably, a different antiviral stimulus, interferon gamma (IFN-γ), that induces a largely non-overlapping set of genes, also transcriptionally represses CDK1, CDK2 and their associated cyclins, resulting in similar dNTP depletion and antiviral effects. Concordantly, the SIV Vpx protein provides complete and partial resistance to the antiviral effects of AhR and IFN-γ, respectively. Thus, distinct antiviral signaling pathways converge on CDK/cyclin repression, causing inhibition of viral DNA synthesis and replication. eLife Sciences Publications, Ltd 2018-08-22 /pmc/articles/PMC6120754/ /pubmed/30132758 http://dx.doi.org/10.7554/eLife.38867 Text en © 2018, Kueck et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Immunology and Inflammation
Kueck, Tonya
Cassella, Elena
Holler, Jessica
Kim, Baek
Bieniasz, Paul D
The aryl hydrocarbon receptor and interferon gamma generate antiviral states via transcriptional repression
title The aryl hydrocarbon receptor and interferon gamma generate antiviral states via transcriptional repression
title_full The aryl hydrocarbon receptor and interferon gamma generate antiviral states via transcriptional repression
title_fullStr The aryl hydrocarbon receptor and interferon gamma generate antiviral states via transcriptional repression
title_full_unstemmed The aryl hydrocarbon receptor and interferon gamma generate antiviral states via transcriptional repression
title_short The aryl hydrocarbon receptor and interferon gamma generate antiviral states via transcriptional repression
title_sort aryl hydrocarbon receptor and interferon gamma generate antiviral states via transcriptional repression
topic Immunology and Inflammation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120754/
https://www.ncbi.nlm.nih.gov/pubmed/30132758
http://dx.doi.org/10.7554/eLife.38867
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