Influenza A Virus Infection Induces Viral and Cellular Defective Ribosomal Products Encoded by Alternative Reading Frames
Autor: | Pierre Faou, Jonathan W. Yewdell, Sara Oveissi, Mubing Duan, Ian G. Barr, Daniel Dlugolenski, John Stambas, Lenny Izzard, Jack R. Bennink, Damien Zanker, Nicole A. Mifsud, Benoît Van den Eynde, Siyuan Wan, David C. Tscharke, Xiaomu Zhang, Nathalie Vigneron, James S. Gibbs, Karen L. Laurie, Weisan Chen, Kun Xiao |
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Přispěvatelé: | UCL - SSS/DDUV/GECE - Génétique cellulaire |
Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
T cell
viruses Immunology Reading frame Epitopes T-Lymphocyte CD8-Positive T-Lymphocytes Viral Nonstructural Proteins medicine.disease_cause Article Epitope Mice Open Reading Frames 03 medical and health sciences 0302 clinical medicine Orthomyxoviridae Infections Influenza Human MHC class I medicine Influenza A virus Animals Humans Immunology and Allergy Immunologic Surveillance Mice Inbred BALB C biology virus diseases Translation (biology) biochemical phenomena metabolism and nutrition Virology Immunosurveillance Alternative Splicing Disease Models Animal Open reading frame HEK293 Cells medicine.anatomical_structure Host-Pathogen Interactions biology.protein 030215 immunology |
Zdroj: | Journal of immunology (Baltimore, Md. : 1950), Vol. 202, no.12, p. 3370-3380 (2019) J Immunol |
Popis: | The 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. |
Databáze: | OpenAIRE |
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