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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-08-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/38867 |
| _version_ | 1811253086545510400 |
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| author | Tonya Kueck Elena Cassella Jessica Holler Baek Kim Paul D Bieniasz |
| author_facet | Tonya Kueck Elena Cassella Jessica Holler Baek Kim Paul D Bieniasz |
| author_sort | Tonya Kueck |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T16:45:29Z |
| format | Article |
| id | doaj.art-bf9fd6772ed746d29ab588e429e4c255 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:45:29Z |
| publishDate | 2018-08-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-bf9fd6772ed746d29ab588e429e4c2552022-12-22T03:24:36ZengeLife Sciences Publications LtdeLife2050-084X2018-08-01710.7554/eLife.38867The aryl hydrocarbon receptor and interferon gamma generate antiviral states via transcriptional repressionTonya Kueck0Elena Cassella1Jessica Holler2Baek Kim3Paul D Bieniasz4https://orcid.org/0000-0002-2368-3719Laboratory of Retrovirology, The Rockefeller University, New York, United StatesLaboratory of Retrovirology, The Rockefeller University, New York, United StatesCenter for Drug Discovery, The Department of Pediatrics, Emory University, Atlanta, United StatesCenter for Drug Discovery, The Department of Pediatrics, Emory University, Atlanta, United States; Department of Pharmacy, Kyung Hee University, Seoul, South KoreaLaboratory of Retrovirology, The Rockefeller University, New York, United States; Howard Hughes Medical Institute, The Rockefeller University, New York, United StatesThe 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.https://elifesciences.org/articles/38867HIV-1aryl hydrocarbon receptorHSVInterferon-gammaSAMDH1 |
| spellingShingle | Tonya Kueck Elena Cassella Jessica Holler Baek Kim Paul D Bieniasz The aryl hydrocarbon receptor and interferon gamma generate antiviral states via transcriptional repression eLife HIV-1 aryl hydrocarbon receptor HSV Interferon-gamma SAMDH1 |
| 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 | HIV-1 aryl hydrocarbon receptor HSV Interferon-gamma SAMDH1 |
| url | https://elifesciences.org/articles/38867 |
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