Journal article
Suppression of the antiviral response by an influenza histone mimic
Nature (London), Vol.483(7390), pp.428-433
03/22/2012
DOI: 10.1038/nature10892
PMCID: PMC3598589
PMID: 22419161
Abstract
Viral infection is commonly associated with virus-driven hijacking of host proteins. Here we describe a novel mechanism by which influenza virus affects host cells through the interaction of influenza non-structural protein 1 (NS1) with the infected cell epigenome. We show that the NS1 protein of influenza A H3N2 subtype possesses a histone-like sequence (histone mimic) that is used by the virus to target the human PAF1 transcription elongation complex (hPAF1C). We demonstrate that binding of NS1 to hPAF1C depends on the NS1 histone mimic and results in suppression of hPAF1C-mediated transcriptional elongation. Furthermore, human PAF1 has a crucial role in the antiviral response. Loss of hPAF1C binding by NS1 attenuates influenza infection, whereas hPAF1C deficiency reduces antiviral gene expression and renders cells more susceptible to viruses. We propose that the histone mimic in NS1 enables the influenza virus to affect inducible gene expression selectively, thus contributing to suppression of the antiviral response.
Details
- Title: Subtitle
- Suppression of the antiviral response by an influenza histone mimic
- Creators
- Ivan Marazzi - Laboratory of Immune Cell Epigenetics and Signaling, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USAJessica S. Y Ho - Laboratory of Immune Cell Epigenetics and Signaling, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USAJaehoon Kim - Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USABalaji Manicassamy - Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1124, New York, New York 10029, USAScott Dewell - Genomics Resource Center, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USARandy A Albrecht - Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1124, New York, New York 10029, USAChris W Seibert - Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1124, New York, New York 10029, USAUwe Schaefer - Laboratory of Immune Cell Epigenetics and Signaling, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USAKate L Jeffrey - Laboratory of Immune Cell Epigenetics and Signaling, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USARab K Prinjha - Epinova DPU, Immuno-Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, UKKevin Lee - Epinova DPU, Immuno-Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, UKAdolfo García-Sastre - Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1124, New York, New York 10029, USARobert G Roeder - Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USAAlexander Tarakhovsky - Laboratory of Immune Cell Epigenetics and Signaling, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.483(7390), pp.428-433
- DOI
- 10.1038/nature10892
- PMID
- 22419161
- PMCID
- PMC3598589
- NLM abbreviation
- Nature
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Grant note
- R01 CA129325 || CA / National Cancer Institute : NCI
- Language
- English
- Date published
- 03/22/2012
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984083876402771
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