Structural and functional analyses reveal promiscuous and species specific use of ephrin receptors by Cedar virus Journal Article


Authors: Laing, E. D.; Navaratnarajah, C. K.; da Silva, S. C.; Petzing, S. R.; Xu, Y.; Sterling, S. L.; Marsh, G. A.; Wang, L. F.; Amaya, M.; Nikolov, D. B.; Cattaneo, R.; Broder, C. C.; Xu, K.
Article Title: Structural and functional analyses reveal promiscuous and species specific use of ephrin receptors by Cedar virus
Abstract: Cedar virus (CedV) is a bat-borne henipavirus related to Nipah virus (NiV) and Hendra virus (HeV), zoonotic agents of fatal human disease. CedV receptor-binding protein (G) shares only ∼30% sequence identity with those of NiV and HeV, although they can all use ephrin-B2 as an entry receptor. We demonstrate that CedV also enters cells through additional B- and A-class ephrins (ephrin-B1, ephrin-A2, and ephrin-A5) and report the crystal structure of the CedV G ectodomain alone and in complex with ephrin-B1 or ephrin-B2. The CedV G receptor-binding site is structurally distinct from other henipaviruses, underlying its capability to accommodate additional ephrin receptors. We also show that CedV can enter cells through mouse ephrin-A1 but not human ephrin-A1, which differ by 1 residue in the key contact region. This is evidence of species specific ephrin receptor usage by a henipavirus, and implicates additional ephrin receptors in potential zoonotic transmission. © 2019 National Academy of Sciences. All rights reserved.
Keywords: ephrins; entry; henipaviruses; cedar virus; virus receptors
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 116
Issue: 41
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2019-10-08
Start Page: 20707
End Page: 20715
Language: English
DOI: 10.1073/pnas.1911773116
PUBMED: 31548390
PROVIDER: scopus
PMCID: PMC6789926
DOI/URL:
Notes: Article -- Export Date: 1 November 2019 -- Source: Scopus
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  1. Dimitar B Nikolov
    86 Nikolov
  2. Kai Xu
    21 Xu