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The neonatal Fc receptor (FcRn) is a pan-arterivirus receptor

Author

Listed:
  • Teressa M. Shaw

    (University of Wisconsin–Madison School of Medicine and Public Health)

  • Devra Huey

    (The Ohio State University
    The Ohio State University)

  • Makky Mousa-Makky

    (The Ohio State University
    The Ohio State University)

  • Jared Compaleo

    (The Ohio State University
    The Ohio State University)

  • Kylie Nennig

    (University of Wisconsin–Madison School of Medicine and Public Health)

  • Aadit P. Shah

    (Stanford University School of Medicine)

  • Fei Jiang

    (The Ohio State University)

  • Xueer Qiu

    (University of Wisconsin–Madison School of Medicine and Public Health)

  • Devon Klipsic

    (University of Wisconsin–Madison)

  • Raymond R. R. Rowland

    (University of Illinois Urbana-Champaign)

  • Igor I. Slukvin

    (University of Wisconsin–Madison School of Medicine and Public Health)

  • Meagan E. Sullender

    (Washington University School of Medicine)

  • Megan T. Baldridge

    (Washington University School of Medicine)

  • Haichang Li

    (The Ohio State University
    The Ohio State University College of Medicine)

  • Cody J. Warren

    (The Ohio State University
    The Ohio State University
    The Ohio State University
    The Ohio State University)

  • Adam L. Bailey

    (University of Wisconsin–Madison School of Medicine and Public Health)

Abstract

Arteriviruses infect a variety of mammalian hosts, but the receptors used by these viruses to enter cells are poorly understood. We identified the neonatal Fc receptor (FcRn) as an important pro-viral host factor via comparative genome-wide CRISPR-knockout screens with multiple arteriviruses. Using a panel of cell lines and divergent arteriviruses, we demonstrate that FcRn is required for the entry step of arterivirus infection and serves as a molecular barrier to arterivirus cross-species infection. We also show that FcRn synergizes with another known arterivirus entry factor, CD163, to mediate arterivirus entry. Overexpression of FcRn and CD163 sensitizes non-permissive cells to infection and enables the culture of fastidious arteriviruses. Treatment of multiple cell lines with a pre-clinical anti-FcRn monoclonal antibody blocked infection and rescued cells from arterivirus-induced death. Altogether, this study identifies FcRn as a novel pan-arterivirus receptor, with implications for arterivirus emergence, cross-species infection, and host-directed pan-arterivirus countermeasure development.

Suggested Citation

  • Teressa M. Shaw & Devra Huey & Makky Mousa-Makky & Jared Compaleo & Kylie Nennig & Aadit P. Shah & Fei Jiang & Xueer Qiu & Devon Klipsic & Raymond R. R. Rowland & Igor I. Slukvin & Meagan E. Sullender, 2024. "The neonatal Fc receptor (FcRn) is a pan-arterivirus receptor," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51142-x
    DOI: 10.1038/s41467-024-51142-x
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    References listed on IDEAS

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