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Title
  • en NS1-binding protein abrogates the elevation of cell viability by the influenza A virus NS1 protein in association with CRKL
Creator
Accessrights open access
Subject
  • Other en NS1
  • Other en CrkL
  • Other en CrkII
  • Other en NS1-BP
  • Other en Cell proliferation
  • Other en ERK
  • NDC 490
Description
  • Abstract en The influenza A virus non-structural protein 1 (NS1) is a multifunctional virulence factor consisting of an RNA binding domain and several Src-homology (SH) 2 and SH3 binding motifs, which promotes virus replication in the host cell and helps to evade antiviral immunity. NS1 modulates general host cell physiology in association with various cellular molecules including NS1-binding protein (NS1-BP) and signaling adapter protein CRK-like (CRKL), while the physiological role of NS1-BP during influenza A virus infection especially in association with NS1 remains unclear. In this study, we analyzed the intracellular association of NS1-BP, NS1 and CRKL to elucidate the physiological roles of these molecules in the host cell. In HEK293T cells, enforced expression of NS1 of A/Beijing (H1N1) and A/Indonesia (H5N1) significantly induced excessive phosphorylation of ERR and elevated cell viability, while the over-expression of NS1-BP and the abrogation of CRKL using siRNA abolished such survival effect of NS1. The pull-down assay using GST-fusion CRKL revealed the formation of intracellular complexes of NS1-BP, NS1 and CRKL. In addition, we identified that the N-terminus SH3 domain of CRKL was essential for binding to NS1-BP using GST-fusion CRKL-truncate mutants. This is the first report to elucidate the novel function of NS1-BP collaborating with viral protein NS1 in modulation of host cell physiology. In addition, an alternative role of adaptor protein CRKL in association with NS1 and NS1-BP during influenza A virus infection is demonstrated. (C) 2013 Elsevier Inc. All rights reserved.
Publisher en Academic press inc elsevier science
Date
    Issued2013-11-29
Language
  • eng
Resource Type journal article
Version Type AM
Identifier HDL http://hdl.handle.net/2115/54561
Relation
  • isVersionOf DOI https://doi.org/10.1016/j.bbrc.2013.11.011
  • PMID 24220336
Journal
    • PISSN 0006-291X
    • NCID AA00564395
      • en Biochemical and biophysical research communications
      • Volume Number441 Issue Number4 Page Start953 Page End957
File
Oaidate 2023-07-26