Influenza A virus infection induces viral and cellular defective ribosomal products encoded by alternative reading frames Academic Article uri icon


  • The importance of antiviral CD8+ T cell recognition of alternative reading frame (ARF)-derived peptides is uncertain. In this study, we describe an epitope (NS1-ARF21-8) present in a predicted 14-residue peptide encoded by the +1 register of NS1 mRNA in the influenza A virus (IAV). NS1-ARF21-8 elicits a robust, highly functional CD8+ T cell response in IAV-infected BALB/c mice. NS1-ARF21-8 is presented from unspliced NS mRNA, likely from downstream initiation on a Met residue that comprises the P1 position of NS1-ARF21-8 Derived from a 14-residue peptide with no apparent biological function and negligible impacts on IAV infection, infectivity, and pathogenicity, NS1-ARF21-8 provides a clear demonstration of how immunosurveillance exploits natural errors in protein translation to provide antiviral immunity. We further show that IAV infection enhances a model cellular ARF translation, which potentially has important implications for virus-induced autoimmunity.


  • Zanker, Damien J
  • Oveissi, Sara
  • Tscharke, David C
  • Duan, Mubing
  • Wan, Siyuan
  • Zhang, Xiaomu
  • Xiao, Kun
  • Mifsud, Nicole A
  • Gibbs, James
  • Izzard, Lenny
  • Dlugolenski, Daniel
  • Faou, Pierre
  • Laurie, Karen L
  • Vigneron, Nathalie
  • Barr, Ian G
  • Stambas, John
  • Van den Eynde, Benoît J
  • Bennink, Jack R
  • Yewdell, Jonathan W
  • Chen, Weisan

publication date

  • 2019