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Journal of Virology, July 2002, p. 7203-7208, Vol. 76, No. 14
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.14.7203-7208.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Disruption of Adherens Junctions Liberates Nectin-1 To Serve as Receptor for Herpes Simplex Virus and Pseudorabies Virus Entry

Miri Yoon and Patricia G. Spear*

Department of Microbiology-Immunology, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611

Received 7 February 2002/ Accepted 24 April 2002

Nectin-1, a cell adhesion molecule belonging to the immunoglobulin superfamily, can bind to virion glycoprotein D (gD) to mediate entry of herpes simplex viruses (HSV) and pseudorabies virus (PRV). Nectin-1 colocalizes with E-cadherin at adherens junctions in epithelial cells. The disruption of cell junctions can result in the redistribution of nectin-1. To determine whether disruption of junctions by calcium depletion influenced the susceptibility of epithelial cells to viral entry, Madin-Darby canine kidney cells expressing endogenous nectin-1 or transfected human nectin-1 were tested for the ability to bind soluble forms of viral gD and to be infected by HSV and PRV, before and after calcium depletion. Confocal microscopy revealed that binding of HSV and PRV gD was localized to adherens junctions in cells maintained in normal medium but was distributed, along with nectin-1, over the entire cell surface after calcium depletion. Both the binding of gD and the fraction of cells that could be infected by HSV-1 and PRV were enhanced by calcium depletion. Taken together, these results provide evidence that nectin-1 confined to adherens junctions in epithelial cells is not very accessible to virus, whereas dissociation of cell junctions releases nectin-1 to serve more efficiently as an entry receptor.

* Corresponding author. Mailing address: Northwestern University, The Feinberg School of Medicine, Department of Microbiology-Immunology, Mail Code S213, Room Ward 6-241, 320 E. Superior St., Chicago, IL 60611. Phone: (312) 503-8230. Fax: (312) 503-1339. E-mail: p-spear{at}northwestern.edu.

Journal of Virology, July 2002, p. 7203-7208, Vol. 76, No. 14
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.14.7203-7208.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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