Format

Send to:

Choose Destination
See comment in PubMed Commons below
Nature. 2012 Mar 14;483(7390):428-33. doi: 10.1038/nature10892.

Suppression of the antiviral response by an influenza histone mimic.

Author information

  • 1Laboratory of Immune Cell Epigenetics and Signaling, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA. imarazzi@rockefeller.edu

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.

PMID:
22419161
[PubMed - indexed for MEDLINE]
PMCID:
PMC3598589
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Write to the Help Desk