The nectin-1alpha transmembrane domain, but not the cytoplasmic tail, influences cell fusion induced by HSV-1 glycoproteins.
Nectin-1 is a receptor for herpes simplex virus (HSV), a member of the immunoglobulin superfamily, and a cellular adhesion molecule. To study domains of nectin-1alpha involved in cell fusion, we measured the ability of nectin-1alpha/nectin-2alpha chimeras, nectin-1alpha/CD4 chimeras, and transmembrane domain and cytoplasmic tail mutants of nectin-1alpha to promote cell fusion induced by HSV-1 glycoproteins. Our results demonstrate that only chimeras and mutants containing the entire V-like domain and a link to the plasma membrane conferred cell-fusion activity. The transmembrane domain and cytoplasmic tail of nectin-1 were not required for any viral receptor or cell adhesion function tested. Cellular cytoplasmic factors that bind to the nectin-1alpha cytoplasmic tail, therefore, did not influence virus entry or cell fusion. Interestingly, the efficiency of cell fusion was reduced when membrane-spanning domains of nectin-1alpha and gD were replaced by glycosylphosphatidylinositol tethers, indicating that transmembrane domains may play a modulatory role in the gD/nectin-1alpha interaction in fusion.
Subramanian
Ravi P
RP
Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, 800 Rose Street, UKMC MS415, Lexington, KY 40536-0298, USA.
Dunn
Jennifer E
JE
Geraghty
Robert J
RJ
D000818:Animals; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002459:Cell Fusion; D006224:Cricetinae; D018259:Herpesvirus 1, Human / Q000737:chemistry*; D000075983:Nectins; D017434:Protein Structure, Tertiary; D014759:Viral Envelope Proteins / Q000378:metabolism* / Q000494:pharmacology; D014764:Viral Proteins / Q000378:metabolism*
D015815:Cell Adhesion Molecules; C000619010:NECTIN1 protein, human; D000075983:Nectins; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C039447:glycoprotein D, Human herpesvirus 1