title: Herpes simplex virus glycoprotein K, but not its syncytial allele, inhibits cell-cell fusion mediated by the four fusogenic glycoproteins, gD, gB, gH, and gL.
abstract: A Myc epitope was inserted at residue 283 of herpes simplex virus type 1 (HSV-1) glycoprotein K (gK), a position previously shown not to interfere with gK activity. The Myc-tagged gK localized predominantly to the endoplasmic reticulum, both in uninfected and in HSV-infected cells. gK, coexpressed with the four HSV fusogenic glycoproteins, gD, gB, gH, and gL, inhibited cell-cell fusion. The effect was partially dose dependent and was observed both in baby hamster kidney (BHK) and in Vero cells, indicating that the antifusion activity of gK may be cell line independent. The antifusion activity of gK did not require viral proteins other than the four fusogenic glycoproteins. A syncytial (syn) allele of gK (syn-gK) carrying the A40V substitution present in HSV-1(MP) did not block fusion to the extent seen with the wild-type (wt) gK, indicating that the syn mutation ablated, at least in part, the antifusogenic activity of wt gK. We conclude that gK is part of the mechanism whereby HSV negatively regulates its own fusion activity. Its effect accounts for the notion that cells infected with wt HSV do not fuse with adjacent, uninfected cells into multinucleated giant cells or syncytia. gK may also function to preclude fusion between virion envelope and the virion-encasing vesicles during virus transport to the extracellular compartment, thus preventing nucleocapsid de-envelopment in the cytoplasm.
authors.affiliation: Department of Experimental Pathology, Section on Microbiology and Virology, University of Bologna, Bologna, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Avitabile
authors.forename: Giulia
authors.initials: G
authors.lastname: Lombardi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Campadelli-Fiume
mesh_terms: D000483:Alleles; D000818:Animals; D002459:Cell Fusion; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D015726:Giant Cells / Q000502:physiology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008561:Membrane Fusion; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
chemical_list: C072448:UL53 protein, Human herpesvirus 1; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C044525:glycoprotein B, herpes simplex virus type 2; C040570:glycoprotein D-herpes simplex virus type 2; C044200:glycoprotein H, herpes simplex virus type 1; C077407:glycoprotein L, Human herpesvirus 1