Journal of Virology, September 1998, p. 7064-7074, Vol. 72, No. 9
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Department of
Microbiology1 and
Center for Oral Health
Research,
Received 27 March 1998/Accepted 20 May 1998
Several cell membrane proteins have been identified as herpes
simplex virus (HSV) entry mediators (Hve). HveA (formerly HVEM) is a
member of the tumor necrosis factor receptor family, whereas the
poliovirus receptor-related proteins 1 and 2 (PRR1 and
PRR2, renamed HveC and HveB) belong to the immunoglobulin superfamily. Here we show that a truncated form of HveC directly binds to HSV glycoprotein D (gD) in solution and at the surface of virions. This
interaction is dependent on the native conformation of gD but
independent of its N-linked glycosylation. Complex formation between
soluble gD and HveC appears to involve one or two gD molecules for one
HveC protein. Since HveA also mediates HSV entry by interacting with
gD, we compared both structurally unrelated receptors for their binding
to gD. Analyses of several gD variants indicated that structure and
accessibility of the N-terminal domain of gD, essential for HveA
binding, was not necessary for HveC interaction. Mutations in
functional regions II, III, and IV of gD had similar effects on binding
to either HveC or HveA. Competition assays with neutralizing anti-gD
monoclonal antibodies (MAbs) showed that MAbs from group Ib prevented
HveC and HveA binding to virions. However, group Ia MAbs blocked HveC
but not HveA binding, and conversely, group VII MAbs blocked HveA but
not HveC binding. Thus, we propose that HSV entry can be mediated by
two structurally unrelated gD receptors through related but not
identical binding with gD.
*
Corresponding author. Mailing address: Department of
Microbiology, School of Dental Medicine, University of Pennsylvania, 4010 Locust St., Philadelphia, PA 19104-6002. Phone: (215) 898-6553. Fax: (215) 898-8385. E-mail:
krumm{at}biochem.dental.upenn.edu.
Present address: Institute for Biochemistry, Swiss Federal
Institute of Technology, Zurich, Switzerland.
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