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

DOI: 10.26508/lsa.201900578 DOI Help

Authors: Rhys Pryce (Wellcome Centre for Human Genetics, University of Oxford) , Kristopher Azarm (Icahn School of Medicine at Mount Sinai) , Ilona Rissanen (Wellcome Centre for Human Genetics, University of Oxford; Helsinki Institute for Life Science, University of Helsinki) , Karl Harlos (Wellcome Centre for Human Genetics, University of Oxford) , Thomas Bowden (Wellcome Centre for Human Genetics, University of Oxford) , Benhur Lee (Icahn School of Medicine at Mount Sinai)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Life Science Alliance , VOL 3

State: Published (Approved)
Published: December 2019
Diamond Proposal Number(s): 19946

Open Access Open Access

Abstract: 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.

Journal Keywords: Structural Biology; Microbiology, Virology & Host Pathogen Interaction

Subject Areas: Biology and Bio-materials


Instruments: I02-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

Documents:
e201900578.full.pdf