Functional studies of host-specific ephrin-B ligands as Henipavirus receptors.

Katharine N Bossart1 Mary Tachedjian Jennifer A McEachern Gary Crameri Zhongyu Zhu Dimiter S Dimitrov Christopher C Broder Lin-Fa Wang
Affiliations 1 institutions
  1. CSIRO Livestock Industries, Australian Animal Health Laboratory, Geelong, Victoria 3220, Australia. [email protected]

Abstract

Hendra virus (HeV) and Nipah virus (NiV) are closely related paramyxoviruses that infect and cause disease in a wide range of mammalian hosts. To determine whether host receptor molecules play a role in species-specific and/or virus-specific infection we have cloned and characterized ephrin-B2 and ephrin-B3 ligands from a range of species, including human, horse, pig, cat, dog, bats (Pteropus alecto and Pteropus vampyrus) and mouse. HeV and NiV were both able to infect cells expressing any of the ephrin-B2 and ephrin-B3 molecules. There did not appear to be significant differences in receptor function from different species or receptor usage by HeV and NiV. Soluble ephrin ligands, their receptors and G-specific human monoclonal antibodies differentially blocked henipavirus infections suggesting different receptor affinities, overlapping receptor binding domains of the henipavirus attachment glycoprotein (G) and that the functional domains of the ephrin ligands may be important for henipavirus binding.

Supporting text Virus Host Location
Amino Acid Sequence 128 Animals 1948 Antibodies, Viral 212 Binding Sites 89 Cell Line 158 Cells, Cultured 26 Cloning, Molecular 16 DNA 2 Ephrin-B2 14 Ephrin-B3 6 Henipavirus 18 Humans 1440 Ligands 5 Molecular Sequence Data 160 Receptors, Virus 204 Species Specificity 84

Evidence records

2 total
Functional Mechanism
2 records · 1 evidence types
Evidence type
2 records
OVE506
Key finding

Hendra virus was able to infect cells expressing ephrin-B2 or ephrin-B3 molecules cloned from multiple mammalian hosts, showing these ligands act as viral receptors.

Virus
Host
Experimental system
Location
Not specified
Supporting text

Hendra virus (HeV) and Nipah virus (NiV) are closely related paramyxoviruses that infect and cause disease in a wide range of mammalian hosts. HeV and NiV were both able to infect cells expressing any of the ephrin-B2 and ephrin-B3 molecules.

Method
cell infection assay using species-specific ephrin-B2 and ephrin-B3 expression | receptor blocking with soluble ligands and monoclonal antibodies
Receptors
ephrin-B2 | ephrin-B3
Host factors
henipavirus G glycoprotein
OVE507
Key finding

Nipah virus was able to infect cells expressing ephrin-B2 or ephrin-B3 molecules cloned from multiple mammalian hosts, showing these ligands act as viral receptors.

Virus
Host
Experimental system
Location
Not specified
Supporting text

Hendra virus (HeV) and Nipah virus (NiV) are closely related paramyxoviruses that infect and cause disease in a wide range of mammalian hosts. HeV and NiV were both able to infect cells expressing any of the ephrin-B2 and ephrin-B3 molecules.

Method
cell infection assay using species-specific ephrin-B2 and ephrin-B3 expression | receptor blocking with soluble ligands and monoclonal antibodies
Receptors
ephrin-B2 | ephrin-B3
Host factors
henipavirus G glycoprotein