Influenza A virus infection induces viral and cellular defective ribosomal products encoded by alternative reading frames

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 Stambas; Benoît J. Van Den Eynde; Jack R. Bennink; Jonathan W. Yewdell; Weisan Chen

doi:10.4049/jimmunol.1900070

Influenza A virus infection induces viral and cellular defective ribosomal products encoded by alternative reading frames

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 Stambas, Benoît J. Van Den Eynde, Jack R. Bennink, Jonathan W. Yewdell, Weisan Chen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

24 Citations (Scopus)

Abstract

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-ARF2_1-8) present in a predicted 14-residue peptide encoded by the +1 register of NS1 mRNA in the influenza A virus (IAV). NS1-ARF2_1-8 elicits a robust, highly functional CD8⁺ T cell response in IAV-infected BALB/c mice. NS1-ARF2_1-8 is presented from unspliced NS mRNA, likely from downstream initiation on a Met residue that comprises the P1 position of NS1-ARF2_1-8. Derived from a 14-residue peptide with no apparent biological function and negligible impacts on IAV infection, infectivity, and pathogenicity, NS1-ARF2_1-8 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.

Original language	English
Pages (from-to)	3370-3380
Number of pages	11
Journal	Journal of Immunology
Volume	202
Issue number	12
DOIs	https://doi.org/10.4049/jimmunol.1900070
Publication status	Published - 15 Jun 2019

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Zanker, D. J., Oveissi, S., Tscharke, D. C., Duan, M., Wan, S., Zhang, X., Xiao, K., Mifsud, N. A., Gibbs, J., Izzard, L., Dlugolenski, D., Faou, P., Laurie, K. L., Vigneron, N., Barr, I. G., Stambas, J., Van Den Eynde, B. J., Bennink, J. R., Yewdell, J. W., & Chen, W. (2019). Influenza A virus infection induces viral and cellular defective ribosomal products encoded by alternative reading frames. Journal of Immunology, 202(12), 3370-3380. https://doi.org/10.4049/jimmunol.1900070

@article{01b0be487837413fade6ed0d06a2ecf2,

title = "Influenza A virus infection induces viral and cellular defective ribosomal products encoded by alternative reading frames",

abstract = "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.",

author = "Zanker, {Damien J.} and Sara Oveissi and Tscharke, {David C.} and Mubing Duan and Siyuan Wan and Xiaomu Zhang and Kun Xiao and Mifsud, {Nicole A.} and James Gibbs and Lenny Izzard and Daniel Dlugolenski and Pierre Faou and Laurie, {Karen L.} and Nathalie Vigneron and Barr, {Ian G.} and John Stambas and {Van Den Eynde}, {Beno{\^i}t J.} and Bennink, {Jack R.} and Yewdell, {Jonathan W.} and Weisan Chen",

note = "Publisher Copyright: Copyright {\textcopyright} 2019 by The American Association of Immunologists, Inc.",

year = "2019",

month = jun,

day = "15",

doi = "10.4049/jimmunol.1900070",

language = "English",

volume = "202",

pages = "3370--3380",

journal = "Journal of Immunology",

issn = "0022-1767",

publisher = "American Association of Immunologists",

number = "12",

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Zanker, DJ, Oveissi, S, Tscharke, DC, Duan, M, Wan, S, Zhang, X, Xiao, K, Mifsud, NA, Gibbs, J, Izzard, L, Dlugolenski, D, Faou, P, Laurie, KL, Vigneron, N, Barr, IG, Stambas, J, Van Den Eynde, BJ, Bennink, JR, Yewdell, JW & Chen, W 2019, 'Influenza A virus infection induces viral and cellular defective ribosomal products encoded by alternative reading frames', Journal of Immunology, vol. 202, no. 12, pp. 3370-3380. https://doi.org/10.4049/jimmunol.1900070

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

SN - 0022-1767

VL - 202

SP - 3370

EP - 3380

JO - Journal of Immunology

JF - Journal of Immunology

IS - 12

ER -

Influenza A virus infection induces viral and cellular defective ribosomal products encoded by alternative reading frames

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