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miR-132 regulates antiviral innate immunity through suppression of the p300 transcriptional co-activator

Lagos, Dimitrios, Pollara, Gabriel, Henderson, Stephen, Gratrix, Fiona, Fabani, Martin, Milne, Richard S.B., Gotch, Frances, Boshoff, Chris·2010·Nature Cell Biology
DOI 10.1038/ncb2054
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Abstract

MicroRNAs are small, non-coding RNAs that negatively regulate gene expression. It has been proposed that microRNAs could function in the regulation of innate immunity, 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 (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.

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Metadata

Authors
Lagos, D., Pollara, G., Henderson, S., Gratrix, F., Fabani, M., Milne, R. S. B., Gotch, F., & Boshoff, C.
Venue
Nature Cell Biology
Publisher
Springer Science and Business Media LLC
Published
2010-04-25
Volume
12
Issue
5
Pages
513-519
ISSN
  • 1465-7392
  • 1476-4679
DOI
10.1038/ncb2054
Cited by
296
References
7
Language
en
Licence
www.springer.com/tdm (tdm)

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