title: The multipartite system that mediates entry of herpes simplex virus into the cell.
abstract: The multipartite entry-fusion system of herpes simplex virus is made of a quartet of glycoproteins-gD, gB, gH.gL-and three alternative gD receptors, herpesvirus entry mediator (HVEM), nectin1 and modified sites on heparan sulphate. This multipartite system recapitulates the basic steps of virus-cell fusion, i.e. receptor recognition, triggering of fusion and fusion execution. Specifically, in addition to serving as the receptor-binding glycoprotein, gD triggers fusion through a specialised domain, named pro-fusion domain (PFD), located C-terminally in the ectodomain. In the unliganded gD the C-terminal region folds around the N-terminal region, such that gD adopts a closed autoinhibited conformation. In HVEM- and nectin1-bound gD the C-terminal region is displaced (opened conformation). gD is the tool for modification of HSV tropism, through insertion of ligands to heterologous tumour-specific receptors. It is discussed whether gD responds to the interaction with the natural and the heterologous receptors by adopting similar conformations, and whether the closed-to-open switch in conformation is a generalised mechanism of activation. A peculiar recombinant highlighted that the central Ig-folded core of gD may not encode executable functions for entry and that the 219-314 aa segment may be sufficient to trigger fusion. With respect to fusion execution, gB appears to be a prospective fusogen based on its coiled-coil trimeric structure, similar to that of another fusion glycoprotein. On the other hand, gH exhibits molecular elements typical of class 1 fusion glycoproteins, in particular heptad repeats and strong tendency to interact with lipids. Whether fusion execution is carried out by gB or gH.gL, or both glycoproteins in complex or sequentially remains to be determined.
authors.affiliation: Department of Experimental Pathology, Section on Microbiology and Virology, Alma Mater Studiorum, University of Bologna, Bologna, Italy. gabriella.campadelli@unibo.it
authors.forename: Gabriella
authors.initials: G
authors.lastname: Campadelli-Fiume
authors.forename: Michele
authors.initials: M
authors.lastname: Amasio
authors.forename: Elisa
authors.initials: E
authors.lastname: Avitabile
authors.forename: Arianna
authors.initials: A
authors.lastname: Cerretani
authors.forename: Cristina
authors.initials: C
authors.lastname: Forghieri
authors.forename: Tatiana
authors.initials: T
authors.lastname: Gianni
authors.forename: Laura
authors.initials: L
authors.lastname: Menotti
mesh_terms: D006023:Glycoproteins / Q000737:chemistry / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D011991:Receptors, Virus / Q000502:physiology; D018139:Simplexvirus / Q000502:physiology*; D015678:Viral Structural Proteins / Q000737:chemistry / Q000502:physiology; D053586:Virus Internalization
chemical_list: D006023:Glycoproteins; D011991:Receptors, Virus; D015678:Viral Structural Proteins