Cell-to-cell spread of wild-type herpes simplex virus type 1, but not of syncytial strains, is mediated by the immunoglobulin-like receptors that mediate virion entry, nectin1 (PRR1/HveC/HIgR) and nectin2 (PRR2/HveB).
The immunoglobulin-like receptors that mediate entry of herpes simplex virus type 1 (HSV-1) into human cells were found to mediate the direct cell-to-cell spread of wild-type virus. The receptors here designated Nectin1alpha and -delta and Nectin2alpha were originally designated HIgR, PRR1/HveC, and PRR2alpha/HveB, respectively. We report the following. (i) Wild-type HSV-1 spreads from cell to cell in J cells expressing nectin1alpha or nectin1delta but not in parental J cells that are devoid of entry receptors. A monoclonal antibody to nectin1, which blocks entry, also blocked cell-to-cell spread in nectin1-expressing J cells. Moreover, wild-type virus did not spread from a receptor-positive to a receptor-negative cell. (ii) The antibody to nectin1 blocked transmission of wild-type virus in a number of human cell lines, with varying efficiencies, suggesting that nectin1 is the principal mediator of wild-type virus spread in a variety of human cell lines. (iii) Nectin1 did not mediate cell fusion induced by the syncytial strains HSV-1(MP) and HFEM-syn. (iv) Nectin2alpha could serve as a receptor for spread of a mutant virus carrying the L25P substitution in glycoprotein D, but not of wild-type virus, in agreement with its ability to mediate entry of the mutant but not of wild-type virus.
Cocchi
F
F
Department of Experimental Pathology, Section on Microbiology and Virology, University of Bologna, 40126 Bologna, Italy.
Menotti
L
L
Dubreuil
P
P
Lopez
M
M
Campadelli-Fiume
G
G
D000911:Antibodies, Monoclonal / Q000276:immunology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D002459:Cell Fusion; D002460:Cell Line; D015726:Giant Cells / Q000502:physiology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D009154:Mutation; D000075983:Nectins; D011991:Receptors, Virus / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D010948:Viral Plaque Assay; D014771:Virion / Q000502:physiology
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; C000619010:NECTIN1 protein, human; D000075983:Nectins; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1