Influenza A Virus Negative Strand RNA Is Translated for CD8+ T Cell Immunosurveillance

J Immunol. 2018 Aug 15;201(4):1222-1228. doi: 10.4049/jimmunol.1800586. Epub 2018 Jul 16.

Abstract

Probing the limits of CD8+ T cell immunosurveillance, we inserted the SIINFEKL peptide into influenza A virus (IAV)-negative strand gene segments. Although IAV genomic RNA is considered noncoding, there is a conserved, relatively long open reading frame present in segment 8, encoding a potential protein termed NEG8. The biosynthesis of NEG8 from IAV has yet to be demonstrated. Although we failed to detect NEG8 protein expression in IAV-infected mouse cells, cell surface Kb-SIINFEKL complexes are generated when SIINFEKL is genetically appended to the predicted C terminus of NEG8, as shown by activation of OT-I T cells in vitro and in vivo. Moreover, recombinant IAV encoding of SIINFEKL embedded in the negative strand of the neuraminidase-stalk coding sequence also activates OT-I T cells in mice. Together, our findings demonstrate both the translation of sequences on the negative strand of a single-stranded RNA virus and its relevance in antiviral immunosurveillance.

Publication types

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

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • HeLa Cells
  • Humans
  • Immunologic Surveillance / immunology*
  • Influenza A virus / genetics*
  • Influenza A virus / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Orthomyxoviridae Infections / immunology
  • Protein Biosynthesis / physiology
  • RNA, Viral / genetics
  • RNA, Viral / immunology*

Substances

  • RNA, Viral