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Influenza A Virus Infection Induces Viral and Cellular Defective Ribosomal Products Encoded by Alternative Reading Frames

tetano

Editor, Senior Moderator
J Immunol. 2019 May 15. pii: ji1900070. doi: 10.4049/jimmunol.1900070. [Epub ahead of print]
[h=1]Influenza A Virus Infection Induces Viral and Cellular Defective Ribosomal Products Encoded by Alternative Reading Frames.[/h] Zanker DJ[SUP]#[/SUP][SUP]1[/SUP], Oveissi S[SUP]#[/SUP][SUP]1[/SUP], Tscharke DC[SUP]2[/SUP], Duan M[SUP]1[/SUP], Wan S[SUP]1[/SUP], Zhang X[SUP]1[/SUP], Xiao K[SUP]1[/SUP], Mifsud NA[SUP]1,[/SUP][SUP]3[/SUP], Gibbs J[SUP]4[/SUP], Izzard L[SUP]5[/SUP], Dlugolenski D[SUP]5[/SUP], Faou P[SUP]1[/SUP], Laurie KL[SUP]6[/SUP], Vigneron N[SUP]7[/SUP], Barr IG[SUP]6[/SUP], Stambas J[SUP]5[/SUP], Van den Eynde BJ[SUP]7[/SUP], Bennink JR[SUP]4[/SUP], Yewdell JW[SUP]#[/SUP][SUP]8[/SUP], Chen W[SUP]#[/SUP][SUP]9[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] The importance of antiviral CD8[SUP]+[/SUP] T cell recognition of alternative reading frame (ARF)-derived peptides is uncertain. In this study, we describe an epitope (NS1-ARF2[SUB]1-8[/SUB]) present in a predicted 14-residue peptide encoded by the +1 register of NS1 mRNA in the influenza A virus (IAV). NS1-ARF2[SUB]1-8[/SUB] elicits a robust, highly functional CD8[SUP]+[/SUP] T cell response in IAV-infected BALB/c mice. NS1-ARF2[SUB]1-8[/SUB] is presented from unspliced NS mRNA, likely from downstream initiation on a Met residue that comprises the P1 position of NS1-ARF2[SUB]1-8[/SUB] Derived from a 14-residue peptide with no apparent biological function and negligible impacts on IAV infection, infectivity, and pathogenicity, NS1-ARF2[SUB]1-8[/SUB] 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.
Copyright ? 2019 by The American Association of Immunologists, Inc.


PMID: 31092636 DOI: 10.4049/jimmunol.1900070
 
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