title: Dissociation of HSV gL from gH by αvβ6- or αvβ8-integrin promotes gH activation and virus entry.
abstract: Herpes simplex virus (HSV) is an important human pathogen. It enters cells through an orchestrated process that requires four essential glycoproteins, gD, gH/gL, and gB, activated in cascade fashion by receptor-binding and signaling. gH/gL heterodimer is conserved across the Herpesviridae family. HSV entry is enabled by gH/gL interaction with αvβ6- or αvβ8-integrin receptors. We report that the interaction of virion gH/gL with integrins resulted in gL dissociation and its release in the medium. gL dissociation occurred if all components of the entry apparatus-receptor-bound gD and gB-were present and was prevented if entry was blocked by a neutralizing monoclonal antibody to gH or by a mutation in gH. We propose that (i) gL dissociation from gH/gL is part of the activation of HSV glycoproteins, critical for HSV entry; and (ii) gL is a functional inhibitor of gH and maintains gH in an inhibited form until receptor-bound gD and integrins signal to gH/gL.
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, Italy.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Gianni
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Massaro
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, Italy gabriella.campadelli@unibo.it.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Campadelli-Fiume
mesh_terms: D020816:Amino Acid Motifs; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000378:metabolism*; D020126:Brefeldin A / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D006561:Herpes Simplex / Q000378:metabolism / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000737:chemistry / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D000075983:Nectins; D017434:Protein Structure, Tertiary; D059748:Proteolysis / Q000187:drug effects; D012995:Solubility; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014771:Virion / Q000187:drug effects / Q000378:metabolism; D053586:Virus Internalization / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D016023:Integrins; D000075983:Nectins; D014759:Viral Envelope Proteins; C044200:glycoprotein H, herpes simplex virus type 1; C077407:glycoprotein L, Human herpesvirus 1; C073878:integrin alphavbeta6; C403414:integrin alphavbeta8; D020126:Brefeldin A
keywords: gH; gL; glycoprotein; herpes simplex virus; virus entry