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CC BY V4.0, Open Access
Journal article
Two key residues in ephrinB3 are critical for its use as an alternative receptor for Nipah virus
PLoS pathogens, Vol.2(2), pp.e7-0086
02/2006
Handle:
https://hdl.handle.net/2376/105281
PMCID: PMC1361355
PMID: 16477309
Abstract
EphrinB2 was recently discovered as a functional receptor for Nipah virus (NiV), a lethal emerging paramyxovirus. Ephrins constitute a class of homologous ligands for the Eph class of receptor tyrosine kinases and exhibit overlapping expression patterns. Thus, we examined whether other ephrins might serve as alternative receptors for NiV. Here, we show that of all known ephrins (ephrinA1-A5 and ephrinB1-B3), only the soluble Fc-fusion proteins of ephrinB3, in addition to ephrinB2, bound to soluble NiV attachment protein G (NiV-G). Soluble NiV-G bound to cell surface ephrinB3 and B2 with subnanomolar affinities (Kd = 0.58 nM and 0.06 nM for ephrinB3 and B2, respectively). Surface plasmon resonance analysis indicated that the relatively lower affinity of NiV-G for ephrinB3 was largely due to a faster off-rate (K(off) = 1.94 x 10(-3) s(-1) versus 1.06 x 10(-4) s(-1) for ephrinB3 and B2, respectively). EphrinB3 was sufficient to allow for viral entry of both pseudotype and live NiV. Soluble ephrinB2 and B3 were able to compete for NiV-envelope-mediated viral entry on both ephrinB2- and B3-expressing cells, suggesting that NiV-G interacts with both ephrinB2 and B3 via an overlapping site. Mutational analysis indicated that the Leu-Trp residues in the solvent exposed G-H loop of ephrinB2 and B3 were critical determinants of NiV binding and entry. Indeed, replacement of the Tyr-Met residues in the homologous positions in ephrinB1 with Leu-Trp conferred NiV receptor activity to ephrinB1. Thus, ephrinB3 is a bona fide alternate receptor for NiV entry, and two residues in the G-H loop of the ephrin B-class ligands are critical determinants of NiV receptor activity.
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Details
- Title
- Two key residues in ephrinB3 are critical for its use as an alternative receptor for Nipah virus
- Creators
- Oscar A Negrete - Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California Los Angeles, California, USAMike C WolfHector C AguilarSven EnterleinWei WangElke MühlbergerStephen V SuAndrea Bertolotti-CiarletRamon FlickBenhur Lee
- Publication Details
- PLoS pathogens, Vol.2(2), pp.e7-0086
- Academic Unit
- Paul G. Allen School for Global Animal Health
- Publisher
- Public Library of Science; United States
- Grant note
- AI07323 / NIAID NIH HHS AI059051 / NIAID NIH HHS R21 AI059051 / NIAID NIH HHS AI060694 / NIAID NIH HHS R01 AI060694 / NIAID NIH HHS P30 CA016042 / NCI NIH HHS GM07185 / NIGMS NIH HHS CA16042 / NCI NIH HHS P30 AI028697 / NIAID NIH HHS T32 AI007323 / NIAID NIH HHS AI28697 / NIAID NIH HHS T32 GM007185 / NIGMS NIH HHS
- Identifiers
- 99900546780301842
- Language
- English
- Resource Type
- Journal article