TY - JOUR
T1 - Structural and functional analyses reveal promiscuous and species specific use of ephrin receptors by Cedar virus
AU - Laing, Eric D.
AU - Navaratnarajah, Chanakha K.
AU - da Silva, Sofia Cheliout
AU - Petzing, Stephanie R.
AU - Xu, Yan
AU - Sterling, Spencer L.
AU - Marsh, Glenn A.
AU - Wang, Lin Fa
AU - Amaya, Moushimi
AU - Nikolov, Dimitar B.
AU - Cattaneo, Roberto
AU - Broder, Christopher C.
AU - Xu, Kai
N1 - Publisher Copyright:
© 2019 National Academy of Sciences. All rights reserved.
PY - 2019/10/8
Y1 - 2019/10/8
N2 - 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.
AB - 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.
KW - Cedar virus
KW - Entry
KW - Ephrins
KW - Henipaviruses
KW - Virus receptors
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U2 - 10.1073/pnas.1911773116
DO - 10.1073/pnas.1911773116
M3 - Article
C2 - 31548390
AN - SCOPUS:85073003986
SN - 0027-8424
VL - 116
SP - 20707
EP - 20715
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 41
ER -