title: Characterization of African bat henipavirus GH-M74a glycoproteins.
abstract: In recent years, novel henipavirus-related sequences have been identified in bats in Africa. To evaluate the potential of African bat henipaviruses to spread in non-bat mammalian cells, we compared the biological functions of the surface glycoproteins G and F of the prototype African henipavirus GH-M74a with those of the glycoproteins of Nipah virus (NiV), a well-characterized pathogenic member of the henipavirus genus. Glycoproteins are central determinants for virus tropism, as efficient binding of henipavirus G proteins to cellular ephrin receptors and functional expression of fusion-competent F proteins are indispensable prerequisites for virus entry and cell-to-cell spread. In this study, we analysed the ability of the GH-M74a G and F proteins to cause cell-to-cell fusion in mammalian cell types readily permissive to NiV or Hendra virus infections. Except for limited syncytium formation in a bat cell line derived from Hypsignathus monstrosus, HypNi/1.1 cells, we did not observe any fusion. The highly restricted fusion activity was predominantly due to the F protein. Whilst GH-M74a G protein was found to interact with the main henipavirus receptor ephrin-B2 and induced syncytia upon co-expression with heterotypic NiV F protein, GH-M74a F protein did not cause evident fusion in the presence of heterotypic NiV G protein. Pulse-chase and surface biotinylation analyses revealed delayed F cleavage kinetics with a reduced expression of cleaved and fusion-active GH-M74a F protein on the cell surface. Thus, the F protein of GH-M74a showed a functional defect that is most likely caused by impaired trafficking leading to less efficient proteolytic activation and surface expression.
authors.affiliation: Institute of Virology, Philipps University Marburg, Marburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Weis
authors.affiliation: Institute of Virology, Philipps University Marburg, Marburg, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Behner
authors.affiliation: Institute of Virology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Hoffmann
authors.affiliation: Institute of Virology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Krüger
authors.affiliation: Institute of Virology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Herrler
authors.affiliation: Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Drosten
authors.affiliation: Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.
authors.forename: Jan Felix
authors.initials: JF
authors.lastname: Drexler
authors.affiliation: Institute of Virology, Philipps University Marburg, Marburg, Germany.
authors.forename: Erik
authors.initials: E
authors.lastname: Dietzel
authors.affiliation: Institute of Virology, Philipps University Marburg, Marburg, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Maisner
mesh_terms: D000349:Africa; D000818:Animals; D002685:Chiroptera / Q000378:metabolism / Q000821:virology*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D045403:Henipavirus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D045464:Henipavirus Infections / Q000378:metabolism / Q000662:veterinary* / Q000821:virology; D045405:Nipah Virus / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C510755:F protein, Nipah virus; D006023:Glycoproteins; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; D014764:Viral Proteins