The KGD motif of Epstein-Barr virus gH/gL is bifunctional, orchestrating infection of B cells and epithelial cells.
Epstein-Barr virus (EBV), a member of the herpesvirus family, is the causative agent of common human infections and specific malignancies. EBV entry into target cells, including B cells and epithelial cells, requires the interaction of multiple virus-encoded glycoproteins. Glycoproteins H and L (gH/gL) cooperate with glycoprotein B (gB) to mediate fusion of the viral envelope with target cell membranes. Both the gH/gL complex and gB are required for fusion, whereas glycoprotein 42 (gp42) acts as a tropism switch and is required for B cell infection and inhibits epithelial cell infection. Our previous studies identified a prominent KGD motif located on the surface of gH/gL. In the current study, we found that this motif serves as a bifunctional domain on the surface of gH/gL that directs EBV fusion of B cells and epithelial cells. Mutation of the KGD motif to AAA decreased fusion with both epithelial and B cells and reduced the binding of gH/gL to epithelial cells and to gp42. We also demonstrate that deletion of amino acids 62 to 66 of gp42 selectively reduces binding to wild-type gH/gL, but not the KGD mutant, suggesting that the KGD motif of gH/gL interacts with the N-terminal amino acids 62 to 66 of gp42.
Department of Microbiology and Immunology, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Jia
J
Chen
Cynthia L
CL
Rowe
Theodore S
TS
Jardetzky
Richard
R
Longnecker
D020816:Amino Acid Motifs; D001402:B-Lymphocytes / Q000821:virology*; D002460:Cell Line; D004847:Epithelial Cells / Q000821:virology*; D020031:Epstein-Barr Virus Infections / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C065527:glycoprotein H, Herpesvirus 4; C103802:glycoprotein L, Human herpesvirus 4