Biology Faculty Articles
Title
Influenza Virus Targets the mRNA Export Machinery and the Nuclear Pore Complex
Document Type
Article
Publication Date
2-6-2007
Publication Title
Proceedings of the National Academy of Sciences of the United States of America
Keywords
NS1, nucleoporin, nuclear transport, mRNA nuclear export
ISSN
1091-6490
Volume
104
Issue/No.
6
First Page
1853
Last Page
1858
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.
NSUWorks Citation
Satterly, Neal; Pei-Ling Tsai; Jan van Deursen; Daniel R. Nussenveig; Yaming Wang; Paula A. Faria Waziry; Agata Levay; David E. Levy; and Beatriz M. A. Fontoura. 2007. "Influenza Virus Targets the mRNA Export Machinery and the Nuclear Pore Complex." Proceedings of the National Academy of Sciences of the United States of America 104, (6): 1853-1858. https://nsuworks.nova.edu/cnso_bio_facarticles/73