title: Attachment protein G of an African bat henipavirus is differentially restricted in chiropteran and nonchiropteran cells.
abstract: Henipaviruses are associated with pteropodid reservoir hosts. The glycoproteins G and F of an African henipavirus (strain M74) have been reported to induce syncytium formation in kidney cells derived from a Hypsignathus monstrosus bat (HypNi/1.1) but not in nonchiropteran BHK-21 and Vero76 cells. Here, we show that syncytia are also induced in two other pteropodid cell lines from Hypsignathus monstrosus and Eidolon helvum bats upon coexpression of the M74 glycoproteins. The G protein was transported to the surface of transfected chiropteran cells, whereas surface expression in the nonchiropteran cells was detectable only in a fraction of cells. In contrast, the G protein of Nipah virus is transported efficiently to the surface of both chiropteran and nonchiropteran cells. Even in chiropteran cells, M74-G was predominantly expressed in the endoplasmic reticulum (ER), as indicated by colocalization with marker proteins. This result is consistent with the finding that all N-glycans of the M74-G proteins are of the mannose-rich type, as indicated by sensitivity to endo H treatment. These data indicate that the surface transport of M74-G is impaired in available cell culture systems, with larger amounts of viral glycoprotein present on chiropteran cells than on nonchiropteran cells. The restricted surface expression of M74-G explains the reduced fusion activity of the glycoproteins of the African henipavirus. Our results suggest strategies for the isolation of infectious viruses, which is necessary to assess the risk of zoonotic virus transmission. Importance: Henipaviruses are highly pathogenic zoonotic viruses associated with pteropodid bat hosts. Whether the recently described African bat henipaviruses have a zoonotic potential as high as that of their Asian and Australian relatives is unknown. We show that surface expression of the attachment protein G of an African henipavirus, M74, is restricted in comparison to the G protein expression of the highly pathogenic Nipah virus. Transport to the cell surface is more restricted in nonchiropteran cells than it is in chiropteran cells, explaining the differential fusion activity of the M74 surface proteins in these cells. Our results imply that surface expression of viral glycoproteins may serve as a major marker to assess the zoonotic risk of emerging henipaviruses.
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: Markus
authors.initials: M
authors.lastname: Hoffmann
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, University of Bonn Medical Centre, Bonn, Germany.
authors.forename: Marcel Alexander
authors.initials: MA
authors.lastname: Müller
authors.affiliation: Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.
authors.forename: Victor Max
authors.initials: VM
authors.lastname: Corman
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 Veterinary Medicine Hannover, Hannover, Germany Georg.Herrler@tiho-hannover.de.
authors.forename: Georg
authors.initials: G
authors.lastname: Herrler
mesh_terms: D000818:Animals; D002451:Cell Compartmentation; D002460:Cell Line; D002685:Chiroptera / Q000821:virology*; D006224:Cricetinae; D005434:Flow Cytometry; D015726:Giant Cells; D045403:Henipavirus / Q000378:metabolism*; D006801:Humans; D013045:Species Specificity; D014759:Viral Envelope Proteins / Q000378:metabolism*
chemical_list: D014759:Viral Envelope Proteins; C116204:attachment protein G
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