Two Key Residues in EphrinB3 Are Critical for Its Use as an Alternative Receptor for Nipah Virus

• DOI: 10.1371/journal.ppat.0020007
• Publication Date: 2006-02-01T14:35:23Z
• Authors: Oscar A Negrete; Mike C Wolf; Hector C Aguilar; Sven Enterlein; Wei Wang; Elke Mühlberger; Stephen V Su; Andrea Bertolotti...; Ramon Flick; Benhur Lee
• Keywords: Ephrin

EphrinB2 was recently discovered as a functional receptor for Nipah virus (NiV), lethal emerging paramyxovirus. Ephrins constitute class of homologous ligands the Eph tyrosine kinases and exhibit overlapping expression patterns. Thus, we examined whether other ephrins might serve alternative receptors NiV. Here, show that all known (ephrinA1-A5 ephrinB1-B3), only soluble Fc-fusion proteins ephrinB3, in addition to ephrinB2, bound NiV attachment protein G (NiV-G). Soluble NiV-G cell surface ephrinB3 B2 with subnanomolar affinities (Kd = 0.58 nM 0.06 B2, respectively). Surface plasmon resonance analysis indicated relatively lower affinity largely due faster off-rate (K(off) 1.94 x 10(-3) s(-1) versus 1.06 10(-4) EphrinB3 sufficient allow viral entry both pseudotype live ephrinB2 B3 were able compete NiV-envelope-mediated on ephrinB2- B3-expressing cells, suggesting interacts via an site. Mutational Leu-Trp residues solvent exposed G-H loop critical determinants binding entry. Indeed, replacement Tyr-Met positions ephrinB1 conferred activity ephrinB1. is bona fide alternate entry, two ephrin B-class are activity.