title: Soluble V domain of Nectin-1/HveC enables entry of herpes simplex virus type 1 (HSV-1) into HSV-resistant cells by binding to viral glycoprotein D.
abstract: Interaction of herpes simplex virus (HSV) glycoprotein D (gD) with specific cellular receptors is essential for HSV infection of susceptible cells. Virus mutants that lack gD can bind to the cell surface (attachment) but do not enter, implying that interaction of gD with its receptor(s) initiates the postattachment (entry) phase of HSV infection. In this report, we have studied HSV entry in the presence of the gD-binding variable (V) domain of the common gD receptor nectin-1/HveC to determine whether cell association of the gD receptor is required for HSV infection. In the presence of increasing amounts of the soluble nectin-1 V domain (sNec1(123)), increasing viral entry into HSV-resistant CHO-K1 cells was observed. At a multiplicity of 3 in the presence of optimal amounts of sNec1(123), approximately 90% of the cells were infected. The soluble V domain of nectin-2, a strain-specific HSV entry receptor, promoted entry of the HSV type 1 (HSV-1) Rid-1 mutant strain, but not of wild-type HSV-1. Preincubation and immunofluorescence studies indicated that free or gD-bound sNec1(123) did not associate with the cell surface. sNec1(123)-mediated entry was highly impaired by interference with the cell-binding activities of viral glycoproteins B and C. While gD has at least two functions, virus attachment to the cell and initiation of the virus entry process, our results demonstrate that the attachment function of gD is dispensable for entry provided that other means of attachment are available, such as gB and gC binding to cell surface glycosaminoglycans.
authors.affiliation: University of Pittsburgh, School of Medicine, Department of Molecular Genetics and Biochemistry, E1246 Biomedical Science Tower, Pittsburgh, PA 15261, USA.
authors.forename: Heechung
authors.initials: H
authors.lastname: Kwon
authors.forename: Qing
authors.initials: Q
authors.lastname: Bai
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Baek
authors.forename: Kelly
authors.initials: K
authors.lastname: Felmet
authors.forename: Edward A
authors.initials: EA
authors.lastname: Burton
authors.forename: William F
authors.initials: WF
authors.lastname: Goins
authors.forename: Justus B
authors.initials: JB
authors.lastname: Cohen
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Glorioso
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000378:metabolism; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D018259:Herpesvirus 1, Human / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D000075983:Nectins; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000914:Antibodies, Viral; D015815:Cell Adhesion Molecules; C000619010:NECTIN1 protein, human; D000075983:Nectins; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1