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 - Funding Information:
Funding for this study was provided from NIH Grants AI054715, AI077995, and AI137813 (to C.C.B.). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. The views expressed in the manuscript are solely those of the authors, and they do not represent official views or opinions of the Department of Defense or the Uniformed Services University of the Health Sciences.
Funding Information:
ACKNOWLEDGMENTS. Funding for this study was provided from NIH Grants AI054715, AI077995, and AI137813 (to C.C.B.). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. The views expressed in the manuscript are solely those of the authors, and they do not represent official views or opinions of the Department of Defense or the Uniformed Services University of the Health Sciences.
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 -