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

Eric D. Laing, Chanakha K. Navaratnarajah, Sofia Cheliout da Silva, Stephanie R. Petzing, Yan Xu, Spencer L. Sterling, Glenn A. Marsh, Lin Fa Wang, Moushimi Amaya, Dimitar B. Nikolov, Roberto Cattaneo, Christopher C. Broder, Kai Xu

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)20707-20715
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number41
DOIs
StatePublished - Oct 8 2019

Fingerprint

Henipavirus
Eph Family Receptors
Ephrin-A1
Ephrin-B1
Ephrin-B2
Hendra Virus
Nipah Virus
Virus Receptors
Zoonoses
Viruses
Ephrin-A2
Ephrin-A5
Ephrins
Virus Attachment
Viral Structures
Carrier Proteins
Binding Sites

Keywords

  • Cedar virus
  • Entry
  • Ephrins
  • Henipaviruses
  • Virus receptors

ASJC Scopus subject areas

  • General

Cite this

Structural and functional analyses reveal promiscuous and species specific use of ephrin receptors by Cedar virus. / Laing, Eric D.; Navaratnarajah, Chanakha K.; da Silva, Sofia Cheliout; Petzing, Stephanie R.; Xu, Yan; Sterling, Spencer L.; Marsh, Glenn A.; Wang, Lin Fa; Amaya, Moushimi; Nikolov, Dimitar B.; Cattaneo, Roberto; Broder, Christopher C.; Xu, Kai.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 116, No. 41, 08.10.2019, p. 20707-20715.

Research output: Contribution to journalArticle

Laing, ED, Navaratnarajah, CK, da Silva, SC, Petzing, SR, Xu, Y, Sterling, SL, Marsh, GA, Wang, LF, Amaya, M, Nikolov, DB, Cattaneo, R, Broder, CC & Xu, K 2019, 'Structural and functional analyses reveal promiscuous and species specific use of ephrin receptors by Cedar virus', Proceedings of the National Academy of Sciences of the United States of America, vol. 116, no. 41, pp. 20707-20715. https://doi.org/10.1073/pnas.1911773116
Laing, Eric D. ; Navaratnarajah, Chanakha K. ; da Silva, Sofia Cheliout ; Petzing, Stephanie R. ; Xu, Yan ; Sterling, Spencer L. ; Marsh, Glenn A. ; Wang, Lin Fa ; Amaya, Moushimi ; Nikolov, Dimitar B. ; Cattaneo, Roberto ; Broder, Christopher C. ; Xu, Kai. / Structural and functional analyses reveal promiscuous and species specific use of ephrin receptors by Cedar virus. In: Proceedings of the National Academy of Sciences of the United States of America. 2019 ; Vol. 116, No. 41. pp. 20707-20715.
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