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

Autor: Rhys Pryce, Benhur Lee, Kristopher D. Azarm, Karl Harlos, Ilona Rissanen, Thomas A. Bowden
Přispěvatelé: Helsinki Institute of Life Science HiLIFE
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Health
Toxicology and Mutagenesis
Plant Science
Plasma protein binding
Ligands
medicine.disease_cause
Protein Structure
Secondary
Interferon
Chiroptera
Chlorocebus aethiops
INFECTION
CRYSTAL-STRUCTURE
Receptor
Research Articles
chemistry.chemical_classification
Henipavirus Infections
Genetics
0303 health sciences
Ecology
biology
Phenotype
Receptors
Virus
Hemagglutinin-neuraminidase
medicine.drug
Research Article
Protein Binding
Henipavirus
HENDRA-VIRUS
Viral protein
TRANSMISSION
030106 microbiology
Ephrin-B2
Ephrin-B1
Transfection
Biochemistry
Genetics and Molecular Biology (miscellaneous)
NIPAH-VIRUS
Virus
03 medical and health sciences
Viral entry
medicine
Animals
Humans
Ephrin
Hendra Virus
Vero Cells
Tropism
HEMAGGLUTININ-NEURAMINIDASE
030304 developmental biology
RECEPTOR
030306 microbiology
HEK 293 cells
RECOGNITION
Virus Internalization
biology.organism_classification
HEK293 Cells
030104 developmental biology
chemistry
BATS
sense organs
3111 Biomedicine
Glycoprotein
Viral Fusion Proteins
ATTACHMENT GLYCOPROTEIN
Zdroj: Life Science Alliance
Popis: An expanded hydrophobic cavity within the structurally constrained receptor-binding site of the Cedar virus attachment glycoprotein facilitates idiosyncratic utilization of ephrin-B1.
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.
Databáze: OpenAIRE
Externí odkaz: