Citations 1
Structural and functional analyses reveal promiscuous and species specific use of ephrin receptors by Cedar virus
Laing, Eric D. , Navaratnarajah, Chanakha K. , Silva, Sofia Cheliout Da, Petzing, Stephanie R., Xu, Yan , Sterling, Spencer L. , Wang, Lin‐Fa , Amaya, Moushimi , Nikolov, Dimitar B. , Cattaneo, Roberto , Broder, Christopher C. , Xu, Kai , Wang, Lin-Fa , Cattaneo, Roberto , Broder, Christopher C , Xu, Kai , Xu, Yan, Marsh, Glenn A.
Proceedings of the National Academy of Sciences | September 23, 2019 | Volume: 116 | Issue: 41 | Pages: 20707-20715
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.