Influenza virus targets the mRNA export machinery and the nuclear pore complex

Neal Satterly, Pei Ling Tsai, Jan Van Deursen, Daniel R. Nussenzveig, Yaming Wang, Paula A. Faria, Agata Levay, David E. Levy, Beatriz M A Fontoura

Research output: Contribution to journalArticle

183 Citations (Scopus)

Abstract

The NS1 protein of influenza A virus is a major virulence factor that is essential for pathogenesis. NS1 functions to impair innate and adaptive immunity by inhibiting host signal transduction and gene expression, but its mechanisms of action remain to be fully elucidated. We show here that NS1 forms an inhibitory complex with NXF1/TAP, p15/NXT, Rae1/mrnp41, and E1B-AP5, which are key constituents of the mRNA export machinery that interact with both mRNAs and nucleoporins to direct mRNAs through the nuclear pore complex. Increased levels of NXF1, p15, or Rae1 revert the mRNA export blockage induced by NS1. Furthermore, influenza virus down-regulates Nup98, a nucleoporin that is a docking site for mRNA export factors. Reduced expression of these mRNA export factors renders cells highly permissive to influenza virus replication, demonstrating that proper levels of key constituents of the mRNA export machinery protect against influenza virus replication. Because Nup98 and Rae1 are induced by interferons, down-regulation of this pathway is likely a viral strategy to promote viral replication. These findings demonstrate previously undescribed influenza-mediated viral-host interactions and provide insights into potential molecular therapies that may interfere with influenza infection.

Original languageEnglish (US)
Pages (from-to)1853-1858
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number6
DOIs
StatePublished - Feb 6 2007

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Nuclear Pore
Orthomyxoviridae
Messenger RNA
Virus Replication
Human Influenza
Down-Regulation
Nuclear Pore Complex Proteins
Adaptive Immunity
Virulence Factors
Innate Immunity
Interferons
Signal Transduction
Gene Expression
Infection

Keywords

  • mRNA nuclear export
  • NS1
  • Nuclear transport
  • Nucleoporin

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Influenza virus targets the mRNA export machinery and the nuclear pore complex. / Satterly, Neal; Tsai, Pei Ling; Van Deursen, Jan; Nussenzveig, Daniel R.; Wang, Yaming; Faria, Paula A.; Levay, Agata; Levy, David E.; Fontoura, Beatriz M A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 6, 06.02.2007, p. 1853-1858.

Research output: Contribution to journalArticle

Satterly, Neal ; Tsai, Pei Ling ; Van Deursen, Jan ; Nussenzveig, Daniel R. ; Wang, Yaming ; Faria, Paula A. ; Levay, Agata ; Levy, David E. ; Fontoura, Beatriz M A. / Influenza virus targets the mRNA export machinery and the nuclear pore complex. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 6. pp. 1853-1858.
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