EphrinB2 is the entry receptor for Nipah virus, an emergent deadly paramyxovirus

Nipah virus, first recognized in 1999, is an emerging disease that causes fatal encephalitis in humans. Its natural host is thought to be the fruit bat but it is also found in pigs and other animals. It could pose a serious threat to the pig-farming industry and there is recent evidence of human-to-human transmission. A crucial receptor that the virus relies on to infect human cells has now been identified, suggesting ways that the infection might be countered by vaccines or drugs. The virus's attachment protein binds to the ephrinB2 receptor. This receptor is critical for normal vascular developmental processes and is present in tissues targeted by Nipah virus. The enzyme EphB4 can block the entry of the virus into the cell. 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 neurons3,4, 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.