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

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

    J Immunol. 2018 Jul 16. pii: ji1800586. doi: 10.4049/jimmunol.1800586. [Epub ahead of print]
    Influenza A Virus Negative Strand RNA Is Translated for CD8+ T Cell Immunosurveillance.

    Hickman HD1, Mays JW1, Gibbs J1, Kosik I1, Mag?dan JG1, Takeda K2, Das S1, Reynoso GV1, Ngudiankama BF1, Wei J1, Shannon JP1, McManus D1, Yewdell JW3.
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    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.


    PMID: 30012850 DOI: 10.4049/jimmunol.1800586
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