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miR-132 regulates antiviral innate immunity through suppression of the p300 transcriptional co-activator
by
Gratrix, Fiona
, Milne, Richard S.B.
, Boshoff, Chris
, Fabani, Martin
, Lagos, Dimitrios
, Gotch, Frances
, Henderson, Stephen
, Pollara, Gabriel
in
631/208/200
/ 631/337/384/331
/ 692/420/2780/262
/ 692/699/255/2514
/ Biomedical and Life Sciences
/ Cancer Research
/ Cell Biology
/ Cells, Cultured
/ Cytomegalovirus - immunology
/ Developmental Biology
/ E1A-Associated p300 Protein - antagonists & inhibitors
/ E1A-Associated p300 Protein - genetics
/ Endothelial Cells - immunology
/ Endothelial Cells - virology
/ Gene expression
/ Gene Expression Regulation - immunology
/ Genetic aspects
/ Herpes simplex virus 1
/ Herpes viruses
/ Herpesviridae - immunology
/ Herpesvirus 1, Human - immunology
/ Herpesvirus 8, Human - immunology
/ Human cytomegalovirus
/ Human herpesvirus 8
/ Humans
/ Immune response
/ Immunity, Innate
/ Infections
/ Kaposi's sarcoma-associated herpesvirus
/ Kaposis sarcoma
/ letter
/ Life Sciences
/ MicroRNAs
/ MicroRNAs - physiology
/ Pathogens
/ Physiological aspects
/ RNA
/ Sarcoma
/ Stem Cells
/ Transcription factors
/ Up-Regulation
/ Viral infections
2010
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miR-132 regulates antiviral innate immunity through suppression of the p300 transcriptional co-activator
by
Gratrix, Fiona
, Milne, Richard S.B.
, Boshoff, Chris
, Fabani, Martin
, Lagos, Dimitrios
, Gotch, Frances
, Henderson, Stephen
, Pollara, Gabriel
in
631/208/200
/ 631/337/384/331
/ 692/420/2780/262
/ 692/699/255/2514
/ Biomedical and Life Sciences
/ Cancer Research
/ Cell Biology
/ Cells, Cultured
/ Cytomegalovirus - immunology
/ Developmental Biology
/ E1A-Associated p300 Protein - antagonists & inhibitors
/ E1A-Associated p300 Protein - genetics
/ Endothelial Cells - immunology
/ Endothelial Cells - virology
/ Gene expression
/ Gene Expression Regulation - immunology
/ Genetic aspects
/ Herpes simplex virus 1
/ Herpes viruses
/ Herpesviridae - immunology
/ Herpesvirus 1, Human - immunology
/ Herpesvirus 8, Human - immunology
/ Human cytomegalovirus
/ Human herpesvirus 8
/ Humans
/ Immune response
/ Immunity, Innate
/ Infections
/ Kaposi's sarcoma-associated herpesvirus
/ Kaposis sarcoma
/ letter
/ Life Sciences
/ MicroRNAs
/ MicroRNAs - physiology
/ Pathogens
/ Physiological aspects
/ RNA
/ Sarcoma
/ Stem Cells
/ Transcription factors
/ Up-Regulation
/ Viral infections
2010
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miR-132 regulates antiviral innate immunity through suppression of the p300 transcriptional co-activator
by
Gratrix, Fiona
, Milne, Richard S.B.
, Boshoff, Chris
, Fabani, Martin
, Lagos, Dimitrios
, Gotch, Frances
, Henderson, Stephen
, Pollara, Gabriel
in
631/208/200
/ 631/337/384/331
/ 692/420/2780/262
/ 692/699/255/2514
/ Biomedical and Life Sciences
/ Cancer Research
/ Cell Biology
/ Cells, Cultured
/ Cytomegalovirus - immunology
/ Developmental Biology
/ E1A-Associated p300 Protein - antagonists & inhibitors
/ E1A-Associated p300 Protein - genetics
/ Endothelial Cells - immunology
/ Endothelial Cells - virology
/ Gene expression
/ Gene Expression Regulation - immunology
/ Genetic aspects
/ Herpes simplex virus 1
/ Herpes viruses
/ Herpesviridae - immunology
/ Herpesvirus 1, Human - immunology
/ Herpesvirus 8, Human - immunology
/ Human cytomegalovirus
/ Human herpesvirus 8
/ Humans
/ Immune response
/ Immunity, Innate
/ Infections
/ Kaposi's sarcoma-associated herpesvirus
/ Kaposis sarcoma
/ letter
/ Life Sciences
/ MicroRNAs
/ MicroRNAs - physiology
/ Pathogens
/ Physiological aspects
/ RNA
/ Sarcoma
/ Stem Cells
/ Transcription factors
/ Up-Regulation
/ Viral infections
2010
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miR-132 regulates antiviral innate immunity through suppression of the p300 transcriptional co-activator
Journal Article
miR-132 regulates antiviral innate immunity through suppression of the p300 transcriptional co-activator
2010
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Overview
Viral infection is shown to trigger CREB-mediated upregulation of miR-132. The interferon response is then downregulated by miR-132 through direct targeting of p300, a transcriptional co-activator, thereby facilitating viral replication.
MicroRNAs are small, non-coding RNAs that negatively regulate gene expression
1
. It has been proposed that microRNAs could function in the regulation of innate immunity
2
,
3
, but this has not been demonstrated for viral infection. Here we test this hypothesis using the human pathogenic virus Kaposi's sarcoma-associated herpesvirus (KSHV) and one of its putative natural cellular targets, primary lymphatic endothelial cells
4
(LECs). We show that an early antiviral microRNA response (6 h post-infection) includes expression of microRNAs that enhance viral gene expression. In particular, the CREB-induced miR-132 microRNA is highly upregulated after infection and has a negative effect on the expression of interferon-stimulated genes, facilitating viral replication. We show a similar function for miR-132 during infection of monocytes with herpes simplex virus-1 (HSV-1) and human cytomegalovirus (HCMV). miR-132 regulates innate antiviral immunity by inhibiting expression of the p300 transcriptional co-activator. p300 is downregulated early after KSHV infection, and inhibition of miR-132 induction restores p300 expression. Furthermore, p300 regulates miR-132 levels, revealing a dynamic equilibrium between miR-132 and p300. By targeting p300, rather than a transcription factor or signalling protein, miR-132 has a broad role in the regulation of antiviral immunity.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Biomedical and Life Sciences
/ Cytomegalovirus - immunology
/ E1A-Associated p300 Protein - antagonists & inhibitors
/ E1A-Associated p300 Protein - genetics
/ Endothelial Cells - immunology
/ Endothelial Cells - virology
/ Gene Expression Regulation - immunology
/ Herpesvirus 1, Human - immunology
/ Herpesvirus 8, Human - immunology
/ Humans
/ Kaposi's sarcoma-associated herpesvirus
/ letter
/ RNA
/ Sarcoma
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