title: Triggering of the newcastle disease virus fusion protein by a chimeric attachment protein that binds to Nipah virus receptors.
abstract: The fusion (F) proteins of Newcastle disease virus (NDV) and Nipah virus (NiV) are both triggered by binding to receptors, mediated in both viruses by a second protein, the attachment protein. However, the hemagglutinin-neuraminidase (HN) attachment protein of NDV recognizes sialic acid receptors, whereas the NiV G attachment protein recognizes ephrinB2/B3 as receptors. Chimeric proteins composed of domains from the two attachment proteins have been evaluated for fusion-promoting activity with each F protein. Chimeras having NiV G-derived globular domains and NDV HN-derived stalks, transmembranes, and cytoplasmic tails are efficiently expressed, bind ephrinB2, and trigger NDV F to promote fusion in Vero cells. Thus, the NDV F protein can be triggered by binding to the NiV receptor, indicating that an aspect of the triggering cascade induced by the binding of HN to sialic acid is conserved in the binding of NiV G to ephrinB2. However, the fusion cascade for triggering NiV F by the G protein and that of triggering NDV F by the chimeras can be distinguished by differential exposure of a receptor-induced conformational epitope. The enhanced exposure of this epitope marks the triggering of NiV F by NiV G but not the triggering of NDV F by the chimeras. Thus, the triggering cascade for NiV G-F fusion may be more complex than that of NDV HN and F. This is consistent with the finding that reciprocal chimeras having NDV HN-derived heads and NiV G-derived stalks, transmembranes, and tails do not trigger either F protein for fusion, despite efficient cell surface expression and receptor binding.
authors: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
authors: Anne M
authors: AM
authors: Mirza
authors: Hector C
authors: HC
authors: Aguilar
authors: Qiyun
authors: Q
authors: Zhu
authors: Paul J
authors: PJ
authors: Mahon
authors: Paul A
authors: PA
authors: Rota
authors: Benhur
authors: B
authors: Lee
authors: Ronald M
authors: RM
authors: Iorio
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D036388:Ephrin-B2 / Q000235:genetics / Q000378:metabolism; D006168:Guinea Pigs; D009522:Newcastle disease virus / Q000235:genetics / Q000378:metabolism*; D045405:Nipah Virus / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D036388:Ephrin-B2; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins