title: The requirements for herpes simplex virus type 1 cell-cell spread via nectin-1 parallel those for virus entry.
abstract: Herpes simplex virus type 1 (HSV-1) spreads from an infected cell to an uninfected cell by virus entry, virus-induced cell fusion, and cell-cell spread. The three forms of virus spread require the viral proteins gB, gD, and gH-gL, as well as a cellular gD receptor. The mutual requirement for the fusion glycoproteins and gD receptor suggests that virus entry, cell fusion, and cell-cell spread occur by a similar mechanism. The goals of this study were to examine the role of the nectin-1alpha transmembrane domain and cytoplasmic tail in cell-cell spread and to obtain a better understanding of the receptor-dependent events occurring at the plasma membrane during cell-cell spread. We determined that an intact nectin-1alpha V-like domain was required for cell-cell spread, while a membrane-spanning domain and cytoplasmic tail were not. Chimeric forms of nectin-1 that were non-functional for virus entry did not mediate cell-cell spread regardless of whether they could mediate cell fusion. Also, cell-cell spread of syncytial isolates was dependent upon nectin-1alpha expression and occurred through a nectin-1-dependent mechanism. Taken together, our results indicate that nectin-1-dependent events occurring at the plasma membrane during cell-cell spread were equivalent to those for virus entry.
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, 800 Rose St., UKMC MS415, Lexington, KY 40536-0298, USA.
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Even
authors.forename: Allison M
authors.initials: AM
authors.lastname: Henley
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Geraghty
mesh_terms: D000818:Animals; D019677:Artificial Gene Fusion; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry / Q000821:virology; D002522:Chlorocebus aethiops; D005434:Flow Cytometry; D017930:Genes, Reporter; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006651:Histocytochemistry; D051379:Mice; D008856:Microscopy, Fluorescence; D000075983:Nectins; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014709:Vero Cells; D001616:beta-Galactosidase / Q000032:analysis / Q000235:genetics
chemical_list: D015815:Cell Adhesion Molecules; C000619010:NECTIN1 protein, human; C000619015:Nectin1 protein, mouse; D000075983:Nectins; D011993:Recombinant Fusion Proteins; D001616:beta-Galactosidase