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

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, Megan T. Baldridge, Haichang Li, Cody J. Warren, Adam L. Bailey

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number6726
JournalNature communications
Volume15
Issue number1
DOIs
StatePublished - Dec 2024

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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