Format

Send to

Choose Destination
Sci Rep. 2018 Feb 1;8(1):2092. doi: 10.1038/s41598-018-20458-2.

SMARCA2-regulated host cell factors are required for MxA restriction of influenza A viruses.

Author information

1
Institute of Virology, Medical Center, University of Freiburg, 79104, Freiburg, Germany.
2
Faculty of Medicine, University of Freiburg, 79104, Freiburg, Germany.
3
Spemann Graduate School of Biology and Medicine, University of Freiburg, 79104, Freiburg, Germany.
4
Faculty of Biology, University of Freiburg, 79104, Freiburg, Germany.
5
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
6
Quantitative Biosciences Institute, QBI, Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, 94158, USA.
7
J. David Gladstone Institutes, San Francisco, CA, 94158, USA.
8
Zymo Research Corp, Irvine, CA, 92614, USA.
9
Sanford Burnham Prebys Medical Discovery Institute, Infectious and Inflammatory Disease Center, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA.
10
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. adolfo.garcia-sastre@mssm.edu.
11
Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. adolfo.garcia-sastre@mssm.edu.
12
Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. adolfo.garcia-sastre@mssm.edu.
13
Institute of Virology, Medical Center, University of Freiburg, 79104, Freiburg, Germany. martin.schwemmle@uniklinik-freiburg.de.
14
Faculty of Medicine, University of Freiburg, 79104, Freiburg, Germany. martin.schwemmle@uniklinik-freiburg.de.
15
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. megan.shaw@mssm.edu.

Abstract

The human interferon (IFN)-induced MxA protein is a key antiviral host restriction factor exhibiting broad antiviral activity against many RNA viruses, including highly pathogenic avian influenza A viruses (IAV) of the H5N1 and H7N7 subtype. To date the mechanism for how MxA exerts its antiviral activity is unclear, however, additional cellular factors are believed to be essential for this activity. To identify MxA cofactors we performed a genome-wide siRNA-based screen in human airway epithelial cells (A549) constitutively expressing MxA using an H5N1 reporter virus. These data were complemented with a proteomic screen to identify MxA-interacting proteins. The combined data identified SMARCA2, the ATPase subunit of the BAF chromatin remodeling complex, as a crucial factor required for the antiviral activity of MxA against IAV. Intriguingly, our data demonstrate that although SMARCA2 is essential for expression of some IFN-stimulated genes (ISGs), and the establishment of an antiviral state, it is not required for expression of MxA, suggesting an indirect effect on MxA activity. Transcriptome analysis of SMARCA2-depleted A549-MxA cells identified a small set of SMARCA2-regulated factors required for activity of MxA, in particular IFITM2 and IGFBP3. These findings reveal that several virus-inducible factors work in concert to enable MxA restriction of IAV.

PMID:
29391557
PMCID:
PMC5794779
DOI:
10.1038/s41598-018-20458-2
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center