Sequence basis for selectivity of ephrin-B2 ligand for Eph receptors and pathogenic henipavirus G glycoproteins

J Virol. 2023 Nov 30;97(11):e0062123. doi: 10.1128/jvi.00621-23. Epub 2023 Oct 16.


Ephrin-B2 (EFNB2) is a ligand for six Eph receptors in humans and regulates multiple cell developmental and signaling processes. It also functions as the cell entry receptor for Nipah virus and Hendra virus, zoonotic viruses that can cause respiratory and/or neurological symptoms in humans with high mortality. Here, we investigate the sequence basis of EFNB2 specificity for binding the Nipah virus attachment G glycoprotein over Eph receptors. We then use this information to engineer EFNB2 as a soluble decoy receptor that specifically binds the attachment glycoproteins of the Nipah virus and other related henipaviruses to neutralize infection. These findings further mechanistic understanding of protein selectivity and may facilitate the development of diagnostics or therapeutics against henipavirus infection.

Keywords: EFNB2; EPH receptors; Hendra virus; Nipah virus; decoy receptor; deep mutational scan; henipavirus; virus entry.

MeSH terms

  • Ephrin-B2* / genetics
  • Ephrin-B2* / metabolism
  • Glycoproteins / metabolism
  • Hendra Virus*
  • Henipavirus Infections*
  • Humans
  • Ligands
  • Nipah Virus*
  • Viral Proteins* / metabolism


  • Ephrin-B2
  • Glycoproteins
  • Ligands
  • Viral Proteins