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Literature detail

A key region of molecular specificity orchestrates unique ephrin-B1 utilization by Cedar virus.

Rhys Pryce1 Kristopher Azarm2 Ilona Rissanen1,3 Karl Harlos1 Thomas A Bowden4 Benhur Lee5,6
Affiliations 6 institutions
  1. Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, UK.
  2. Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  3. Helsinki Institute for Life Science, University of Helsinki, Biocenter 3, Helsinki, Finland.
  4. Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, UK [email protected].
  5. Icahn School of Medicine at Mount Sinai, New York, NY, USA [email protected].
  6. Global Virus Network Center of Excellence, Center for Virology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
PMID 31862858 2020 Life Sci Alliance eng epublish
PubMed DOI Browse context

Article

Publication summary

The emergent zoonotic henipaviruses, Hendra, and Nipah are responsible for frequent and fatal disease outbreaks in domestic animals and humans. Specificity of henipavirus attachment glycoproteins (G) for highly species-conserved ephrin ligands underpins their broad host range and is associated with systemic and neurological disease pathologies. Here, we demonstrate that Cedar virus (CedV)-a related henipavirus that is ostensibly nonpathogenic-possesses an idiosyncratic entry receptor repertoire that includes the common henipaviral receptor, ephrin-B2, but, distinct from pathogenic henipaviruses, does not include ephrin-B3. Uniquely among known henipaviruses, CedV can use ephrin-B1 for cellular entry. Structural analyses of CedV-G reveal a key region of molecular specificity that directs ephrin-B1 utilization, while preserving a universal mode of ephrin-B2 recognition. The structural and functional insights presented uncover diversity within the known henipavirus receptor repertoire and suggest that only modest structural changes may be required to modulate receptor specificities within this group of lethal human pathogens.

Virus Internalization Animals Chiroptera Chlorocebus aethiops Ephrin-B1 Ephrin-B2 HEK293 Cells Henipavirus Henipavirus Infections Humans Ligands Protein Binding Protein Structure, Secondary Receptors, Virus Transfection Vero Cells Viral Fusion Proteins EFNB1 protein, human

Structured evidence records

Evidence records

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

Cedar virus binds and utilizes ephrin-B1 and ephrin-B2 for cell entry, unlike other henipaviruses that use ephrin-B2 and ephrin-B3.

Virus
CedV
Host
Not specified
Location
Not specified
Supporting text

Cedar virus (CedV) possesses an idiosyncratic entry receptor repertoire that includes the common henipaviral receptor, ephrin-B2, but, distinct from pathogenic henipaviruses, does not include ephrin-B3. Uniquely among known henipaviruses, CedV can use ephrin-B1 for cellular entry.

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

Cedar virus retains ephrin-B2 binding while lacking ephrin-B3 recognition, showing divergence in receptor repertoire relative to other henipaviruses.

Virus
CedV
Host
Not specified
Location
Not specified
Supporting text

Cedar virus (CedV) possesses an idiosyncratic entry receptor repertoire that includes the common henipaviral receptor, ephrin-B2, but, distinct from pathogenic henipaviruses, does not include ephrin-B3.

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

Cedar virus does not utilize ephrin-B3 as an entry receptor, in contrast to other pathogenic henipaviruses.

Virus
CedV
Host
Not specified
Location
Not specified
Supporting text

Cedar virus (CedV) possesses an idiosyncratic entry receptor repertoire that includes the common henipaviral receptor, ephrin-B2, but, distinct from pathogenic henipaviruses, does not include ephrin-B3.

Method
structural analysis; cell-entry assay
Receptors
ephrin-B3
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

Cedar virus attachment glycoprotein G contains a molecular region that enables binding to ephrin-B1 in addition to the common ephrin-B2 receptor, distinguishing it from pathogenic henipaviruses and altering receptor usage.

Virus
CedV
Host
Not specified
Location
Not specified
Supporting text

Structural analyses of CedV-G reveal a key region of molecular specificity that directs ephrin-B1 utilization, while preserving a universal mode of ephrin-B2 recognition.

Genes or proteins
G glycoprotein
Receptors
ephrin-B1; ephrin-B2
Mechanism types
receptor_binding; cell_entry