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J Virol, July 1998, p. 5802-5810, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

HveA (Herpesvirus Entry Mediator A), a Coreceptor for Herpes Simplex Virus Entry, also Participates in Virus-Induced Cell Fusion

Tracy Terry-Allison,1 Rebecca I. Montgomery,1 J. Charles Whitbeck,2,3,4 Ruliang Xu,2,3,4 Gary H. Cohen,2,3 Roselyn J. Eisenberg,3,4 and Patricia G. Spear1,*

Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611,1 and School of Dental Medicine,2 Center for Oral Health Research,3 and School of Veterinary Medicine,4 University of Pennsylvania, Philadelphia, Pennsylvania 19104

Received 24 November 1997/Accepted 7 April 1998

The purpose of this study was to determine whether a cell surface protein that can serve as coreceptor for herpes simplex virus type 1 (HSV-1) entry, herpesvirus entry mediator (previously designated HVEM but renamed HveA), also mediates HSV-1-induced cell-cell fusion. We found that transfection of DNA from KOS-804, a previously described HSV-1 syncytial (Syn) strain whose Syn mutation was mapped to an amino acid substitution in gK, induced numerous large syncytia on HveA-expressing Chinese hamster ovary cells (CHO-HVEM12) but not on control cells (CHO-C8). Antibodies specific for gD as well as for HveA were effective inhibitors of KOS-804-induced fusion, consistent with previously described direct interactions between gD and HveA. Since mutations in gD determine the ability of HSV-1 to utilize HveA for entry, we examined whether the form of virally expressed gD also influenced the ability of HveA to mediate fusion. We produced a recombinant virus carrying the KOS-804 Syn mutation and the KOS-Rid1 gD mutation, which significantly reduces viral entry via HveA, and designated it KOS-SR1. KOS-SR1 DNA had a markedly reduced ability to induce syncytia on CHO-HVEM12 cells and a somewhat enhanced ability to induce syncytia on CHO-C8 cells. These results support previous findings concerning the relative abilities of KOS and KOS-Rid1 to infect CHO-HVEM12 and CHO-C8 cells. Thus, HveA mediates cell-cell fusion as well as viral entry and both activities of HveA are contingent upon the form of gD expressed by the virus.

* Corresponding author. Mailing address: Department of Microbiology-Immunology, Northwestern University Medical School, Ward Memorial Building, 303 East Chicago Ave., Chicago, IL 60611-3008. Phone: (312) 503-8230. Fax: (312) 503-1339. E-mail: p-spear{at}nwu.edu.

J Virol, July 1998, p. 5802-5810, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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