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Quantitative proteomics defines mechanisms of antiviral defence and cell death during modified vaccinia Ankara infection

Author

Listed:
  • Jonas D. Albarnaz

    (University of Cambridge
    University of Cambridge
    The Pirbright Institute)

  • Joanne Kite

    (University of Cambridge
    University of Cambridge)

  • Marisa Oliveira

    (University of Cambridge
    University of Cambridge)

  • Hanqi Li

    (University of Cambridge
    University of Cambridge)

  • Ying Di

    (University of Cambridge
    University of Cambridge)

  • Maria H. Christensen

    (University of Bonn)

  • Joao A. Paulo

    (Harvard Medical School)

  • Robin Antrobus

    (University of Cambridge
    University of Cambridge)

  • Steven P. Gygi

    (Harvard Medical School)

  • Florian I. Schmidt

    (University of Bonn)

  • Edward L. Huttlin

    (Harvard Medical School)

  • Geoffrey L. Smith

    (University of Cambridge
    University of Oxford)

  • Michael P. Weekes

    (University of Cambridge
    University of Cambridge)

Abstract

Modified vaccinia Ankara (MVA) virus does not replicate in human cells and is the vaccine deployed to curb the current outbreak of mpox. Here, we conduct a multiplexed proteomic analysis to quantify >9000 cellular and ~80% of viral proteins throughout MVA infection of human fibroblasts and macrophages. >690 human proteins are down-regulated >2-fold by MVA, revealing a substantial remodelling of the host proteome. >25% of these MVA targets are not shared with replication-competent vaccinia. Viral intermediate/late gene expression is necessary for MVA antagonism of innate immunity, and suppression of interferon effectors such as ISG20 potentiates virus gene expression. Proteomic changes specific to infection of macrophages indicate modulation of the inflammatory response, including inflammasome activation. Our approach thus provides a global view of the impact of MVA on the human proteome and identifies mechanisms that may underpin its abortive infection. These discoveries will prove vital to design future generations of vaccines.

Suggested Citation

  • Jonas D. Albarnaz & Joanne Kite & Marisa Oliveira & Hanqi Li & Ying Di & Maria H. Christensen & Joao A. Paulo & Robin Antrobus & Steven P. Gygi & Florian I. Schmidt & Edward L. Huttlin & Geoffrey L. S, 2023. "Quantitative proteomics defines mechanisms of antiviral defence and cell death during modified vaccinia Ankara infection," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43299-8
    DOI: 10.1038/s41467-023-43299-8
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    References listed on IDEAS

    as
    1. Denisa Bojkova & Kevin Klann & Benjamin Koch & Marek Widera & David Krause & Sandra Ciesek & Jindrich Cinatl & Christian Münch, 2020. "Proteomics of SARS-CoV-2-infected host cells reveals therapy targets," Nature, Nature, vol. 583(7816), pages 469-472, July.
    2. Veit Hornung & Andrea Ablasser & Marie Charrel-Dennis & Franz Bauernfeind & Gabor Horvath & Daniel. R. Caffrey & Eicke Latz & Katherine A. Fitzgerald, 2009. "AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC," Nature, Nature, vol. 458(7237), pages 514-518, March.
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