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


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.

SUBMITTER: Hickman HD 

PROVIDER: S-EPMC6082381 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Influenza A Virus Negative Strand RNA Is Translated for CD8<sup>+</sup> T Cell Immunosurveillance.

Hickman Heather D HD   Mays Jacqueline W JW   Gibbs James J   Kosik Ivan I   Magadán Javier G JG   Takeda Kazuyo K   Das Suman S   Reynoso Glennys V GV   Ngudiankama Barbara F BF   Wei JiaJie J   Shannon John P JP   McManus Daniel D   Yewdell Jonathan W JW  

Journal of immunology (Baltimore, Md. : 1950) 20180716 4


Probing the limits of CD8<sup>+</sup> 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 K<sup>b</sup>-  ...[more]

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