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

tetano

Editor, Senior Moderator
J Immunol. 2018 Jul 16. pii: ji1800586. doi: 10.4049/jimmunol.1800586. [Epub ahead of print]
[h=1]Influenza A Virus Negative Strand RNA Is Translated for CD8[SUP]+[/SUP] T Cell Immunosurveillance.[/h] Hickman HD[SUP]1[/SUP], Mays JW[SUP]1[/SUP], Gibbs J[SUP]1[/SUP], Kosik I[SUP]1[/SUP], Mag?dan JG[SUP]1[/SUP], Takeda K[SUP]2[/SUP], Das S[SUP]1[/SUP], Reynoso GV[SUP]1[/SUP], Ngudiankama BF[SUP]1[/SUP], Wei J[SUP]1[/SUP], Shannon JP[SUP]1[/SUP], McManus D[SUP]1[/SUP], Yewdell JW[SUP]3[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] 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]-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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