hnRNP A2/B1 interacts with influenza A viral protein NS1 and inhibits virus replication potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nuclear export

Virology. 2014 Jan 20:449:53-61. doi: 10.1016/j.virol.2013.11.009. Epub 2013 Nov 26.

Abstract

The NS1 protein of influenza viruses is a major virulence factor and exerts its function through interacting with viral/cellular RNAs and proteins. In this study, we identified heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) as an interacting partner of NS1 proteins by a proteomic method. Knockdown of hnRNP A2/B1 by small interfering RNA (siRNA) resulted in higher levels of NS vRNA, NS1 mRNA, and NS1 protein in the virus-infected cells. In addition, we demonstrated that hnRNP A2/B1 proteins are associated with NS1 and NS2 mRNAs and that knockdown of hnRNP A2/B1 promotes transport of NS1 mRNA from the nucleus to the cytoplasm in the infected cells. Lastly, we showed that knockdown of hnRNP A2/B1 leads to enhanced virus replication. Our results suggest that hnRNP A2/B1 plays an inhibitory role in the replication of influenza A virus in host cells potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nucleocytoplasmic translocation.

Keywords: Influenza A virus; NS1; Protein–protein interaction; Proteomics; hnRNP A2/B1; mRNA nuclear export.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Active Transport, Cell Nucleus
  • Cell Line
  • Cell Nucleus / metabolism
  • Cell Nucleus / virology
  • Down-Regulation
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / genetics
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / metabolism*
  • Humans
  • Influenza A Virus, H1N1 Subtype / genetics
  • Influenza A Virus, H1N1 Subtype / metabolism*
  • Influenza, Human / genetics
  • Influenza, Human / metabolism*
  • Influenza, Human / virology
  • Protein Binding
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Viral / genetics
  • RNA, Viral / metabolism*
  • Viral Nonstructural Proteins / genetics*
  • Viral Nonstructural Proteins / metabolism*
  • Virus Replication*

Substances

  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B
  • INS1 protein, influenza virus
  • RNA, Messenger
  • RNA, Viral
  • Viral Nonstructural Proteins
  • hnRNP A2