TY - JOUR
T1 - Influenza A virus infection induces viral and cellular defective ribosomal products encoded by alternative reading frames
AU - Zanker, Damien J.
AU - Oveissi, Sara
AU - Tscharke, David C.
AU - Duan, Mubing
AU - Wan, Siyuan
AU - Zhang, Xiaomu
AU - Xiao, Kun
AU - Mifsud, Nicole A.
AU - Gibbs, James
AU - Izzard, Lenny
AU - Dlugolenski, Daniel
AU - Faou, Pierre
AU - Laurie, Karen L.
AU - Vigneron, Nathalie
AU - Barr, Ian G.
AU - Stambas, John
AU - Van Den Eynde, Benoît J.
AU - Bennink, Jack R.
AU - Yewdell, Jonathan W.
AU - Chen, Weisan
PY - 2019/6/15
Y1 - 2019/6/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85067219326&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1900070
DO - 10.4049/jimmunol.1900070
M3 - Article
C2 - 31092636
AN - SCOPUS:85067219326
VL - 202
SP - 3370
EP - 3380
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 12
ER -