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

Krishna K. Narayanan, Moushimi Amaya, Natalie Tsang, Randy Yin, Alka Jays, Christopher C. Broder, Diwakar Shukla, Erik Procko

Research output: Contribution to journalArticlepeer-review

Abstract

IMPORTANCE: 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.

Original languageEnglish (US)
Pages (from-to)e0062123
JournalJournal of virology
Volume97
Issue number11
DOIs
StatePublished - Nov 30 2023

Keywords

  • EFNB2
  • EPH receptors
  • Hendra virus
  • Nipah virus
  • decoy receptor
  • deep mutational scan
  • henipavirus
  • virus entry

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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