stambas-influenzaavirus-2019.pdf (1.84 MB)
Influenza A virus infection induces viral and cellular defective ribosomal products encoded by alternative reading frames
journal contribution
posted on 2019-06-15, 00:00 authored by Damien J Zanker, Sara Oveissi, David C Tscharke, Mubing Duan, Siyuan Wan, Xiaomu Zhang, Kun Xiao, Nicole A Mifsud, James Gibbs, Lenny Izzard, Daniel Dlugolenski, Pierre Faou, Karen L Laurie, Nathalie Vigneron, Ian G Barr, John StambasJohn Stambas, Benoît J Van den Eynde, Jack R Bennink, Jonathan W Yewdell, Weisan ChenThe importance of antiviral CD8+ T cell recognition of alternative reading frame (ARF)-derived peptides is uncertain. In this study, we describe an epitope (NS1-ARF21-8) present in a predicted 14-residue peptide encoded by the +1 register of NS1 mRNA in the influenza A virus (IAV). NS1-ARF21-8 elicits a robust, highly functional CD8+ T cell response in IAV-infected BALB/c mice. NS1-ARF21-8 is presented from unspliced NS mRNA, likely from downstream initiation on a Met residue that comprises the P1 position of NS1-ARF21-8 Derived from a 14-residue peptide with no apparent biological function and negligible impacts on IAV infection, infectivity, and pathogenicity, NS1-ARF21-8 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.
History
Journal
Journal of immunologyVolume
202Issue
12Pagination
3370 - 3380Publisher
American Association of ImmunologistsLocation
Bethesda, Md.Publisher DOI
Link to full text
eISSN
1550-6606Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2019, The American Association of Immunologists, Inc.Usage metrics
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Keywords
influenza A virus (IAV)antiviral CD8+ T cell recognitionalternative reading frame (ARF)–derived peptidesepitope (NS1-ARF21–8)IAV-infected BALB\/c micevirus-induced autoimmunityScience & TechnologyLife Sciences & BiomedicineImmunologyMHC CLASS-INUCLEAR TRANSLATIONANTIGENIC PEPTIDEINITIATION CODONNS1 PROTEINIMMUNODOMINANCEEPITOPEIDENTIFICATIONRESPONSESDETERMINANTSImmunology
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