OmniVira

Literature detail

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

Eric D Laing1 Chanakha K Navaratnarajah2 Sofia Cheliout Da Silva1 Stephanie R Petzing1 Yan Xu3 Spencer L Sterling1 Glenn A Marsh4 Lin-Fa Wang5 Moushimi Amaya1 Dimitar B Nikolov3 Roberto Cattaneo2 Christopher C Broder6,7 Kai Xu8,7
Affiliations 8 institutions
  1. Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
  2. Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905.
  3. Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065.
  4. Commonwealth Scientific and Industrial Research Organization Australian Animal Health Laboratory, Geelong, VIC 3219, Australia.
  5. Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore 169857.
  6. Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814
  7. [email protected] [email protected].
  8. Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065
PMID 31548390 2019 Proc Natl Acad Sci U S A eng ppublish
PubMed DOI Browse context

Article

Publication summary

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.

Cedar virus entry ephrins henipaviruses virus receptors Animals Cell Fusion Ephrin-B1 Ephrin-B2 Ephrin-B3 Henipavirus Henipavirus Infections Humans Mice Mutation Protein Binding Protein Conformation Receptors, Virus

Structured evidence records

Evidence records

4 total
Receptor Usage 3 records
Receptor Usage Extraction confidence 1.00
Key finding

Cedar virus (CedV) uses ephrin-B2, ephrin-B1, ephrin-A2, and ephrin-A5 receptors for cell entry, supported by structural analysis of CedV G in complex with ephrin-B1 and ephrin-B2.

Virus
CedV
Host
Not specified
Location
Not specified
Supporting text

Cedar virus (CedV) ... 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.

Method
crystal structure; cell entry assay
Receptors
ephrin-B2
Receptor Usage Extraction confidence 1.00
Key finding

Cedar virus (CedV) can enter cells using multiple ephrin receptors, including ephrin-B1, ephrin-A2, and ephrin-A5.

Virus
CedV
Host
Not specified
Location
Not specified
Supporting text

We demonstrate that CedV also enters cells through additional B- and A-class ephrins (ephrin-B1, ephrin-A2, and ephrin-A5).

Method
cell entry assay
Receptors
ephrin-B1
Receptor Usage Extraction confidence 1.00
Key finding

Cedar virus enters cells via mouse ephrin-A1 but not human ephrin-A1, indicating species-specific receptor usage dependent on a single residue difference.

Virus
CedV
Location
Not specified
Supporting text

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.

Method
cell entry assay
Receptors
ephrin-A1
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.90
Key finding

Cedar virus glycoprotein G is structurally distinct, enabling use of multiple ephrin receptors and species-specific binding to mouse but not human ephrin-A1 due to a single amino acid difference.

Virus
CedV
Host
Not specified
Location
Not specified
Supporting text

Cedar virus (CedV) ... enters cells through additional B- and A-class ephrins (ephrin-B1, ephrin-A2, and ephrin-A5) ... The CedV G receptor-binding site is structurally distinct from other henipaviruses ... CedV can enter cells through mouse ephrin-A1 but not human ephrin-A1, which differ by 1 residue in the key contact region.

Genes or proteins
G; ephrin-B1; ephrin-B2; ephrin-A2; ephrin-A5; ephrin-A1
Receptors
ephrin-B1; ephrin-B2; ephrin-A2; ephrin-A5; ephrin-A1
Mechanism types
receptor_binding; cell_entry; species_specificity