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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
Proceedings of the National Academy of Sciences of the United States of America | 2019

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.

Pubmed ID: 31548390

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: R01 AI054715
  • Agency: NCI NIH HHS, United States
    Id: P30 CA008748
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS038486
  • Agency: NIAID NIH HHS, United States
    Id: R21 AI137813
  • Agency: NIAID NIH HHS, United States
    Id: U01 AI077995

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Clustal Omega (tool)

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RRID:SCR_001672

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