1. Department of Microbiology, Immunology and Molecular Genetics,
2. Department of Pathology and Laboratory Medicine,
3. UCLA AIDS Institute, David Geffen School of Medicine, UCLA, Los Angeles, California 90095, USA
4. Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA

Correspondence to: Benhur Lee^1,2,3 Correspondence and requests for materials should be addressed to B.L. (Email: bleebhl@ucla.edu).

Nipah virus (NiV) is an emergent paramyxovirus that causes fatal encephalitis in up to 70 per cent of infected patients¹, and there is evidence of human–to–human transmission². Endothelial syncytia, comprised of multinucleated giant-endothelial cells, are frequently found in NiV infections, and are mediated by the fusion (F) and attachment (G) envelope glycoproteins. Identification of the receptor for this virus will shed light on the pathobiology of NiV infection, and spur the rational development of effective therapeutics. Here we report that ephrinB2, the membrane-bound ligand for the EphB class of receptor tyrosine kinases (RTKs)³, specifically binds to the attachment (G) glycoprotein of NiV. Soluble Fc-fusion proteins of ephrinB2, but not ephrinB1, effectively block NiV fusion and entry into permissive cell types. Moreover, transfection of ephrinB2 into non-permissive cells renders them permissive for NiV fusion and entry. EphrinB2 is expressed on endothelial cells and neurons^{3, 4}, which is consistent with the known cellular tropism for NiV⁵. Significantly, we find that NiV-envelope-mediated infection of microvascular endothelial cells and primary cortical rat neurons is inhibited by soluble ephrinB2, but not by the related ephrinB1 protein. Cumulatively, our data show that ephrinB2 is a functional receptor for NiV.

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