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

  • Nat Commun. 2024 Aug 7;15(1):6726. doi: 10.1038/s41467-024-51142-x.
Teressa M Shaw  1 ,  Devra Huey  2  3 ,  Makky Mousa-Makky  2  3 ,  Jared Compaleo  2  3 ,  Kylie Nennig  1 ,  Aadit P Shah  4 ,  Fei Jiang  2 ,  Xueer Qiu  1 ,  Devon Klipsic  5 ,  Raymond R R Rowland  6 ,  Igor I Slukvin  1 ,  Meagan E Sullender  7 ,  Megan T Baldridge  7 ,  Haichang Li  2  8 ,  Cody J Warren  #  9  10  11  12 ,  Adam L Bailey  #  13
Affiliations
  • 1. Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.
  • 2. Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, 43210, USA.
  • 3. Viruses and Emerging Pathogens Program, Infectious Diseases Institute, The Ohio State University, Columbus, OH, USA.
  • 4. Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • 5. Research Animal Resources and Compliance (RARC), University of Wisconsin-Madison, Madison, WI, USA.
  • 6. Department of Pathobiology, College of Veterinary Medicine, University of Illinois Urbana-Champaign, Urbana, IL, USA.
  • 7. Division of Infectious Diseases, Department of Medicine, Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • 8. Department of Surgery, The Ohio State University College of Medicine, Columbus, OH, 43210, USA.
  • 9. Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, 43210, USA. [email protected].
  • 10. Viruses and Emerging Pathogens Program, Infectious Diseases Institute, The Ohio State University, Columbus, OH, USA. [email protected].
  • 11. Center for RNA Biology, The Ohio State University, Columbus, OH, USA. [email protected].
  • 12. Center for Retrovirus Research, The Ohio State University, Columbus, OH, USA. [email protected].
  • 13. Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA. [email protected].
  • # Contributed equally.
PMID: 39112502 DOI: 10.1038/s41467-024-51142-x
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.

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