Comparative usage of herpesvirus entry mediator A and nectin-1 by laboratory strains and clinical isolates of herpes simplex virus.

Abstract

The herpesvirus entry mediator A (HVEM/HveA) and nectin-1 (HveC/CD111) are two major receptors for herpes simplex virus (HSV). Although structurally unrelated, both receptors can independently mediate entry of wild-type (wt) HSV-1 and HSV-2 by interacting with the viral envelope glycoprotein D (gD). Laboratory strains with defined mutations in gD (e.g. rid1) do not use HVEM but use nectin-2 (HveB/CD112) for entry. The relative usage of HVEM and nectin-1 during HSV infection in vivo is not known. In the absence of a defined in vivo model, we used in vitro approaches to address this question. First, we screened HSV clinical isolates from various origins for receptor tropism and found that all used both HVEM and nectin-1. Second, we determined the numbers of surface receptors on various susceptible and resistant cell lines as well as on primary fibroblasts derived from an individual with cleft lip/palate ectodermal dysplasia (CLPED1). Although CLPED1 cells can only express a defective form of nectin-1, they allowed entry of wild type and mutant HSV strains by usage of either HVEM or nectin-2. Finally, we compared the ability of HVEM and nectin-1 to mediate entry when expressed at varying cell surface densities. Both receptors showed a direct relationship between the number of receptors and HSV susceptibility. Direct comparison of receptors suggests that nectin-1 is more efficient at promoting entry than HVEM. Overall, our data suggest that both receptors play a role during HSV infection in vivo and that both are highly efficient even at low levels of expression.

• Authors: Claude Krummenacher, Frédéric Baribaud, Manuel Ponce de Leon, Isabelle Baribaud, J Charles Whitbeck, Ruliang Xu, Gary H Cohen, Roselyn J Eisenberg
• Journal: Virology (Virology) Vol. 322 Issue 2 Pg. 286-99 (May 01 2004) ISSN: 0042-6822 [Print] United States
• PMID: 15110526 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cell Adhesion Molecules
• NECTIN1 protein, human
• Nectin1 protein, mouse
• Nectins
• Receptors, Tumor Necrosis Factor
• Receptors, Tumor Necrosis Factor, Member 14
• Receptors, Virus
• TNFRSF14 protein, human
• Tnfrsf14 protein, mouse
• Viral Envelope Proteins
• glycoprotein D, Human herpesvirus 1

Topics

• Animals
• CHO Cells
• Cell Adhesion Molecules (metabolism)
• Cell Line
• Cricetinae
• Herpes Simplex (virology)
• Herpesvirus 1, Human (genetics, pathogenicity, physiology)
• Humans
• Laboratories
• Mice
• Mutation
• Nectins
• Receptors, Tumor Necrosis Factor (metabolism)
• Receptors, Tumor Necrosis Factor, Member 14
• Receptors, Virus (metabolism)
• Viral Envelope Proteins (genetics, metabolism)