title: Structural basis for Epstein-Barr virus host cell tropism mediated by gp42 and gHgL entry glycoproteins.
abstract: Herpesvirus entry into host cells is mediated by multiple virally encoded receptor binding and membrane fusion glycoproteins. Despite their importance in host cell tropism and associated disease pathology, the underlying and essential interactions between these viral glycoproteins remain poorly understood. For Epstein-Barr virus (EBV), gHgL/gp42 complexes bind HLA class II to activate membrane fusion with B cells, but gp42 inhibits fusion and entry into epithelial cells. To clarify the mechanism by which gp42 controls the cell specificity of EBV infection, here we determined the structure of gHgL/gp42 complex bound to an anti-gHgL antibody (E1D1). The critical regulator of EBV tropism is the gp42 N-terminal domain, which tethers the HLA-binding domain to gHgL by wrapping around the exterior of three gH domains. Both the gp42 N-terminal domain and E1D1 selectively inhibit epithelial-cell fusion; however, they engage distinct surfaces of gHgL. These observations clarify key determinants of EBV host cell tropism.
authors.affiliation: Department of Structural Biology, Stanford University School of Medicine, 1201 Welch Road, Stanford, California 94305.
authors.forename: Karthik
authors.identifier: 0000-0002-5736-8709
authors.initials: K
authors.lastname: Sathiyamoorthy
authors.affiliation: Department of Structural Biology, Stanford University School of Medicine, 1201 Welch Road, Stanford, California 94305.
authors.forename: Yao Xiong
authors.initials: YX
authors.lastname: Hu
authors.affiliation: Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Ward 6-Northeast Corner 6-255/254, 303 East Chicago Avenue, Chicago, Illinois 60611.
authors.forename: Britta S
authors.initials: BS
authors.lastname: Möhl
authors.affiliation: Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Ward 6-Northeast Corner 6-255/254, 303 East Chicago Avenue, Chicago, Illinois 60611.
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Ward 6-Northeast Corner 6-255/254, 303 East Chicago Avenue, Chicago, Illinois 60611.
authors.forename: Richard
authors.initials: R
authors.lastname: Longnecker
authors.affiliation: Department of Structural Biology, Stanford University School of Medicine, 1201 Welch Road, Stanford, California 94305.
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Jardetzky
mesh_terms: D000818:Animals; D016466:CHO Cells; D003412:Cricetulus; D004847:Epithelial Cells / Q000821:virology; D004854:Herpesvirus 4, Human / Q000737:chemistry / Q000502:physiology*; D009154:Mutation; D011487:Protein Conformation; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000502:physiology*; D056189:Viral Tropism
chemical_list: D014759:Viral Envelope Proteins