Acute emergence and reversion of influenza A virus quasispecies within CD8+ T cell antigenic peptides

Sophie A Valkenburg, Sergio Quinones-Parra, Stephanie Gras, Naomi Komadina, Jodie McVernon, Zhongfang Fang Wang, Noor Hanim Abd Halim, Pina Iannello, Catherine Cole, Karen L Laurie, Anne Kelso, Jamie Rossjohn, Peter C Doherty, Stephen J Turner, Katherine Kedzierska

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Influenza A virus-specific CD8(+) cytotoxic T lymphocytes (CTLs) provide a degree of cross-strain protection that is potentially subverted by mutation. Here we describe the sequential emergence of such variants within CTL epitopes for a persistently infected, immunocompromised infant. Further analysis in immunodeficient and wild-type mice supports the view that CTL escape variants arise frequently in influenza, accumulate with time and revert in the absence of immune pressure under MHCI-mismatched conditions. Viral fitness, the abundance of endogenous CD8(+) T cell responses and T cell receptor repertoire diversity influence the nature of these de novo mutants. Structural characterization of dominant escape variants shows how the peptide-MHCI interaction is modified to affect variant-MHCI stability. The mechanism of influenza virus escape thus looks comparable to that recognized for chronic RNA viruses like HIV and HCV, suggesting that immunocompromised patients with prolonged viral infection could have an important part in the emergence of influenza quasispecies.
Original languageEnglish
Article number3663
Number of pages10
JournalNature Communications
Volume4
DOIs
Publication statusPublished - 2013

Cite this

Valkenburg, S. A., Quinones-Parra, S., Gras, S., Komadina, N., McVernon, J., Wang, Z. F., ... Kedzierska, K. (2013). Acute emergence and reversion of influenza A virus quasispecies within CD8+ T cell antigenic peptides. Nature Communications, 4, [3663]. https://doi.org/10.1038/ncomms3663
Valkenburg, Sophie A ; Quinones-Parra, Sergio ; Gras, Stephanie ; Komadina, Naomi ; McVernon, Jodie ; Wang, Zhongfang Fang ; Abd Halim, Noor Hanim ; Iannello, Pina ; Cole, Catherine ; Laurie, Karen L ; Kelso, Anne ; Rossjohn, Jamie ; Doherty, Peter C ; Turner, Stephen J ; Kedzierska, Katherine. / Acute emergence and reversion of influenza A virus quasispecies within CD8+ T cell antigenic peptides. In: Nature Communications. 2013 ; Vol. 4.
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title = "Acute emergence and reversion of influenza A virus quasispecies within CD8+ T cell antigenic peptides",
abstract = "Influenza A virus-specific CD8(+) cytotoxic T lymphocytes (CTLs) provide a degree of cross-strain protection that is potentially subverted by mutation. Here we describe the sequential emergence of such variants within CTL epitopes for a persistently infected, immunocompromised infant. Further analysis in immunodeficient and wild-type mice supports the view that CTL escape variants arise frequently in influenza, accumulate with time and revert in the absence of immune pressure under MHCI-mismatched conditions. Viral fitness, the abundance of endogenous CD8(+) T cell responses and T cell receptor repertoire diversity influence the nature of these de novo mutants. Structural characterization of dominant escape variants shows how the peptide-MHCI interaction is modified to affect variant-MHCI stability. The mechanism of influenza virus escape thus looks comparable to that recognized for chronic RNA viruses like HIV and HCV, suggesting that immunocompromised patients with prolonged viral infection could have an important part in the emergence of influenza quasispecies.",
author = "Valkenburg, {Sophie A} and Sergio Quinones-Parra and Stephanie Gras and Naomi Komadina and Jodie McVernon and Wang, {Zhongfang Fang} and {Abd Halim}, {Noor Hanim} and Pina Iannello and Catherine Cole and Laurie, {Karen L} and Anne Kelso and Jamie Rossjohn and Doherty, {Peter C} and Turner, {Stephen J} and Katherine Kedzierska",
year = "2013",
doi = "10.1038/ncomms3663",
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journal = "Nature Communications",
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Valkenburg, SA, Quinones-Parra, S, Gras, S, Komadina, N, McVernon, J, Wang, ZF, Abd Halim, NH, Iannello, P, Cole, C, Laurie, KL, Kelso, A, Rossjohn, J, Doherty, PC, Turner, SJ & Kedzierska, K 2013, 'Acute emergence and reversion of influenza A virus quasispecies within CD8+ T cell antigenic peptides' Nature Communications, vol. 4, 3663. https://doi.org/10.1038/ncomms3663

Acute emergence and reversion of influenza A virus quasispecies within CD8+ T cell antigenic peptides. / Valkenburg, Sophie A; Quinones-Parra, Sergio; Gras, Stephanie; Komadina, Naomi; McVernon, Jodie; Wang, Zhongfang Fang; Abd Halim, Noor Hanim; Iannello, Pina; Cole, Catherine; Laurie, Karen L; Kelso, Anne; Rossjohn, Jamie; Doherty, Peter C; Turner, Stephen J; Kedzierska, Katherine.

In: Nature Communications, Vol. 4, 3663, 2013.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Acute emergence and reversion of influenza A virus quasispecies within CD8+ T cell antigenic peptides

AU - Valkenburg, Sophie A

AU - Quinones-Parra, Sergio

AU - Gras, Stephanie

AU - Komadina, Naomi

AU - McVernon, Jodie

AU - Wang, Zhongfang Fang

AU - Abd Halim, Noor Hanim

AU - Iannello, Pina

AU - Cole, Catherine

AU - Laurie, Karen L

AU - Kelso, Anne

AU - Rossjohn, Jamie

AU - Doherty, Peter C

AU - Turner, Stephen J

AU - Kedzierska, Katherine

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AB - Influenza A virus-specific CD8(+) cytotoxic T lymphocytes (CTLs) provide a degree of cross-strain protection that is potentially subverted by mutation. Here we describe the sequential emergence of such variants within CTL epitopes for a persistently infected, immunocompromised infant. Further analysis in immunodeficient and wild-type mice supports the view that CTL escape variants arise frequently in influenza, accumulate with time and revert in the absence of immune pressure under MHCI-mismatched conditions. Viral fitness, the abundance of endogenous CD8(+) T cell responses and T cell receptor repertoire diversity influence the nature of these de novo mutants. Structural characterization of dominant escape variants shows how the peptide-MHCI interaction is modified to affect variant-MHCI stability. The mechanism of influenza virus escape thus looks comparable to that recognized for chronic RNA viruses like HIV and HCV, suggesting that immunocompromised patients with prolonged viral infection could have an important part in the emergence of influenza quasispecies.

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JO - Nature Communications

JF - Nature Communications

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