Nature. Suppression of the antiviral response by an influenza histone mimic

[Giuseppe]

[Source: Nature, full text: (LINK). Abstract, edited.]

Suppression of the antiviral response by an influenza histone mimic


Ivan Marazzi,<SUP>1 </SUP>Jessica S. Y. Ho,<SUP>1 </SUP>Jaehoon Kim,<SUP>2 </SUP>Balaji Manicassamy,<SUP>3, 4 </SUP>Scott Dewell,<SUP>5 </SUP>Randy A. Albrecht,<SUP>3, 4 </SUP>Chris W. Seibert,<SUP>3 </SUP>Uwe Schaefer,<SUP>1 </SUP>Kate L. Jeffrey,<SUP>1 </SUP>Rab K. Prinjha,<SUP>6 </SUP>Kevin Lee,<SUP>6 </SUP>Adolfo Garc?a-Sastre,<SUP>3, 4, 7 </SUP>Robert G. Roeder<SUP>2 </SUP>& Alexander Tarakhovsky<SUP>1</SUP>
<SUP></SUP>
Journal name: Nature, Volume: 483, Pages: 428?433
Date published: (22 March 2012)

DOI: doi:10.1038/nature10892

Received: 07 September 2011, Accepted: 23 January 2012, Published online: 14 March 2012



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.
​

Subject terms: Biochemistry Immunology Cell biology Virology

​

-
------

 

[Shiloh]

Re: Nature. Suppression of the antiviral response by an influenza histone mimic

Source: http://newswire.rockefeller.edu/2012/04/23/influenza-“histone-mimic”-suppresses-antiviral-response/

Influenza ?histone mimic? suppresses antiviral response
April 23, 2012 | Science News

For a virus like influenza, the key to success isn?t in overpowering the immune system, it?s in tricking it. A team of researchers led by scientists at The Rockefeller University has identified a novel mechanism by which influenza viruses hijack key regulators of the human body?s normal antiviral response in order to slip by it undetected. The finding, reported recently in Nature, shows that the immunosuppressive NS1 protein of the influenza A virus mimics a core component of gene regulating machinery in order to block antiviral gene function. The results they describe have major implications for our understanding of the biology of the seasonal influenza virus and its pathogenesis. The research also suggests a possible target for a new class of antiviral and anti-inflammatory drugs...