title: A soluble form of Epstein-Barr virus gH/gL inhibits EBV-induced membrane fusion and does not function in fusion.
abstract: We investigated whether soluble EBV gH/gL (sgH/gL) functions in fusion and made a series of truncations of gH/gL domains based on the gH/gL crystal structure. We found sgH/gL failed to mediate cell-cell fusion both when co-expressed with the other entry glycoproteins and when added exogenously to fusion assays. Interestingly, sgH/gL inhibited cell-cell fusion in a dose dependent manner when co-expressed. sgH/gL from HSV was unable to inhibit EBV fusion, suggesting the inhibition was specific to EBV gH/gL. sgH/gL stably binds gp42, but not gB nor gH/gL. The domain mutants, DI/gL, DI-II/gL and DI-II-III/gL were unable to bind gp42. Instead, DI-II/gL, DI-II-III/gL and sgH/gL but not DI/gL decreased the expression of gp42, resulting in decreased overall fusion. Overall, our results suggest that domain IV may be required for proper folding and the transmembrane domain and cytoplasmic tail of EBV gH/gL are required for the most efficient fusion.
authors.affiliation: Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States.
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Rowe
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Connolly
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Jardetzky
authors.forename: Richard
authors.initials: R
authors.lastname: Longnecker
mesh_terms: D000818:Animals; D016466:CHO Cells; D002459:Cell Fusion; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D006224:Cricetinae; D004854:Herpesvirus 4, Human / Q000502:physiology*; D008561:Membrane Fusion / Q000502:physiology*; D011485:Protein Binding; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism*; D053585:Virus Attachment
chemical_list: D014759:Viral Envelope Proteins