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APOBEC3B drives PKR-mediated translation shutdown and protects stress granules in response to viral infection

Author

Listed:
  • Lavanya Manjunath

    (University of California Irvine
    University of California Irvine
    University of California Irvine)

  • Sunwoo Oh

    (University of California Irvine
    University of California Irvine
    University of California Irvine)

  • Pedro Ortega

    (University of California Irvine
    University of California Irvine
    University of California Irvine)

  • Alexis Bouin

    (University of California Irvine
    University of California Irvine)

  • Elodie Bournique

    (University of California Irvine
    University of California Irvine
    University of California Irvine)

  • Ambrocio Sanchez

    (University of California Irvine
    University of California Irvine
    University of California Irvine)

  • Pia Møller Martensen

    (Aarhus University)

  • Ashley A. Auerbach

    (University of Texas Health San Antonio
    University of Minnesota – Twin Cities)

  • Jordan T. Becker

    (University of Minnesota – Twin Cities
    University of Minnesota – Twin Cities)

  • Marcus Seldin

    (University of California Irvine
    University of California Irvine)

  • Reuben S. Harris

    (University of Texas Health San Antonio
    University of Texas Health San Antonio)

  • Bert L. Semler

    (University of California Irvine
    University of California Irvine)

  • Rémi Buisson

    (University of California Irvine
    University of California Irvine
    University of California Irvine
    University of California Irvine)

Abstract

Double-stranded RNA produced during viral replication and transcription activates both protein kinase R (PKR) and ribonuclease L (RNase L), which limits viral gene expression and replication through host shutoff of translation. In this study, we find that APOBEC3B forms a complex with PABPC1 to stimulate PKR and counterbalances the PKR-suppressing activity of ADAR1 in response to infection by many types of viruses. This leads to translational blockage and the formation of stress granules. Furthermore, we show that APOBEC3B localizes to stress granules through the interaction with PABPC1. APOBEC3B facilitates the formation of protein-RNA condensates with stress granule assembly factor (G3BP1) by protecting mRNA associated with stress granules from RNAse L-induced RNA cleavage during viral infection. These results not only reveal that APOBEC3B is a key regulator of different steps of the innate immune response throughout viral infection but also highlight an alternative mechanism by which APOBEC3B can impact virus replication without editing viral genomes.

Suggested Citation

  • Lavanya Manjunath & Sunwoo Oh & Pedro Ortega & Alexis Bouin & Elodie Bournique & Ambrocio Sanchez & Pia Møller Martensen & Ashley A. Auerbach & Jordan T. Becker & Marcus Seldin & Reuben S. Harris & Be, 2023. "APOBEC3B drives PKR-mediated translation shutdown and protects stress granules in response to viral infection," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36445-9
    DOI: 10.1038/s41467-023-36445-9
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