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Journal of Virology, April 2000, p. 3909-3917, Vol. 74, No. 8
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

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)

Francesca Cocchi,1 Laura Menotti,1 Patrice Dubreuil,2 Marc Lopez,2 and Gabriella Campadelli-Fiume1,*

Department of Experimental Pathology, Section on Microbiology and Virology, University of Bologna, 40126 Bologna, Italy,1 and Institute of Cancerology and Immunology, INSERM U.119, 13009 Marseille, France2

Received 2 December 1999/Accepted 20 January 2000

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.

* Corresponding author. Mailing address: Dipartimento di Patologia Sperimentale, Sezione di Microbiologia e Virologia, Via San Giacomo, 12, 40126 Bologna, Italy. Phone: 39 51 2094733/34. Fax: 39 51 2094747. E-mail: campadel{at}alma.unibo.it.

Journal of Virology, April 2000, p. 3909-3917, Vol. 74, No. 8
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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