Identification of novel amino acid residues of influenza virus PA-X that are important for PA-X shutoff activity by using yeast

Virology. 2018 Mar:516:71-75. doi: 10.1016/j.virol.2018.01.004. Epub 2018 Jan 10.

Abstract

The influenza A virus protein PA-X comprises an N-terminal PA region and a C-terminal PA-X-specific region. PA-X suppresses host gene expression, termed shutoff, via mRNA cleavage. Although the endonuclease active site in the N-terminal PA region of PA-X and basic amino acids in the C-terminal PA-X-specific region are known to be important for PA-X shutoff activity, other amino acids may also play a role. Here, we used yeast to identify novel amino acids of PA-X that are important for PA-X shutoff activity. Unlike wild-type PA-X, most PA-X mutants predominantly localized in the cytoplasm, indicating that these mutations decreased the shutoff activity of PA-X by affecting PA-X translocation to the nucleus. Mapping of the identified amino acids onto the N-terminal structure of PA revealed that some of them likely contribute to the formation of the endonuclease active site of PA.

Keywords: Influenza; PA-X; Shutoff; Yeasts.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Host-Pathogen Interactions
  • Humans
  • Influenza A Virus, H1N1 Subtype / chemistry
  • Influenza A Virus, H1N1 Subtype / enzymology*
  • Influenza A Virus, H1N1 Subtype / genetics
  • Influenza, Human / genetics*
  • Influenza, Human / virology
  • Molecular Sequence Data
  • Protein Binding
  • Protein Transport
  • Repressor Proteins / chemistry*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Viral Nonstructural Proteins / chemistry*
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / metabolism*

Substances

  • PA-X protein, influenza A virus
  • Repressor Proteins
  • Viral Nonstructural Proteins