2. Academic Validation
  3. The neonatal Fc receptor (FcRn) is a pan-arterivirus receptor

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

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. warren.802@osu.edu.
  • 10 Viruses and Emerging Pathogens Program, Infectious Diseases Institute, The Ohio State University, Columbus, OH, USA. warren.802@osu.edu.
  • 11 Center for RNA Biology, The Ohio State University, Columbus, OH, USA. warren.802@osu.edu.
  • 12 Center for Retrovirus Research, The Ohio State University, Columbus, OH, USA. warren.802@osu.edu.
  • 13 Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA. albailey@wisc.edu.
  • # 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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