title: Overexpression of gK in gK-transformed cells collapses the Golgi apparatus into the endoplasmic reticulum inhibiting virion egress, glycoprotein transport, and virus-induced cell fusion.
abstract: Intracellular transport and egress of alphaherpesviruses require the coordinate function of multiple proteins and glycoproteins. Recently, we showed that gK is expressed on infected cell surfaces and that gK cell-surface expression required the presence of the UL20 protein [J. Virol. 77 (2003), 499]. Overexpression of gK by gK-transformed cells blocked transport of enveloped virions from perinuclear spaces and inhibited virus-induced cell fusion caused by gK syncytial mutants [J. Virol. 69 (1995), 5401]. Therefore, we investigated whether altered synthesis and transport of gK was responsible for the observed gK-mediated interference phenomena. HSV-1 infection of the gK-transformed cell line Vero (gK9) caused a profound entrapment of gK in the endoplasmic reticulum and total inhibition of gK cell surface expression. In addition, gK drastically inhibited intracellular transport and maturation of gD and caused substantial defects in Golgi-dependent glycosylation of gB. Visualization of intracellular organelles via confocal microscopy revealed a profound collapse of the Golgi apparatus into the endoplasmic reticulum. These results were analogous to those observed in the presence of brefeldin A, a known Golgi disruptor. Therefore, virion entrapment within perinuclear spaces and inhibition of glycoprotein transport are due to gK-mediated collapse of the Golgi apparatus.
authors.affiliation: Division of Biotechnology and Molecular Medicine, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Foster
authors.forename: Galena V
authors.initials: GV
authors.lastname: Rybachuk
authors.forename: Xavier
authors.initials: X
authors.lastname: Alvarez
authors.forename: Olga
authors.initials: O
authors.lastname: Borkhsenious
authors.forename: Konstantin G
authors.initials: KG
authors.lastname: Kousoulas
mesh_terms: D000818:Animals; D002459:Cell Fusion; D002461:Cell Line, Transformed; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000502:physiology; D006023:Glycoproteins / Q000378:metabolism*; D006056:Golgi Apparatus / Q000502:physiology*; D018259:Herpesvirus 1, Human / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D014162:Transfection; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D006023:Glycoproteins; C072448:UL53 protein, Human herpesvirus 1; D014759:Viral Envelope Proteins; D014764:Viral Proteins