Ephrin-B2 expression critically influences Nipah virus infection independent of its cytoplasmic tail.
BACKGROUND
Cell entry and cell-to-cell spread of the highly pathogenic Nipah virus (NiV) requires binding of the NiV G protein to cellular ephrin receptors and subsequent NiV F-mediated fusion. Since expression levels of the main NiV entry receptor ephrin-B2 (EB2) are highly regulated in vivo to fulfill the physiological functions in axon guidance and angiogenesis, the goal of this study was to determine if changes in the EB2 expression influence NiV infection.


RESULTS
Surprisingly, transfection of increasing EB2 plasmid concentrations reduced cell-to-cell fusion both in cells expressing the NiV glycoproteins and in cells infected with NiV. This effect was attributed to the downregulation of the NiV glycoproteins from the cell surface. In addition to the influence on cell-to-cell fusion, increased EB2 expression significantly reduced the total amount of NiV-infected cells, thus interfered with virus entry. To determine if the negative effect of elevated EB2 expression on virus entry is a result of an increased EB2 signaling, receptor function of a tail-truncated and therefore signaling-defective DeltacEB2 was tested. Interestingly, DeltacEB2 fully functioned as NiV entry and fusion receptor, and overexpression also interfered with virus replication.


CONCLUSIONS
Our findings clearly show that EB2 signaling does not account for the striking negative impact of elevated receptor expression on NiV infection, but rather that the ratio between the NiV envelope glycoproteins and surface receptors critically influence cell-to-cell fusion and virus entry.
Thiel
Lena
L
Institute of Virology, Philipps University of Marburg, Marburg, Germany. thiellen@staff.uni-marburg.de
Diederich
Sandra
S
Erbar
Stephanie
S
Pfaff
Dennis
D
Augustin
Hellmut G
HG
Maisner
Andrea
A
D000818:Animals; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism; D015536:Down-Regulation; D036388:Ephrin-B2 / Q000096:biosynthesis* / Q000235:genetics; D006367:HeLa Cells; D045464:Henipavirus Infections / Q000378:metabolism* / Q000821:virology; D006801:Humans; D045405:Nipah Virus / Q000378:metabolism / Q000502:physiology*; D011991:Receptors, Virus / Q000096:biosynthesis* / Q000235:genetics; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000378:metabolism; D053585:Virus Attachment; D053586:Virus Internalization
D036388:Ephrin-B2; D011991:Receptors, Virus; D014759:Viral Envelope Proteins