Herpesvirus entry mediator and nectin-1 mediate herpes simplex virus 1 infection of the murine cornea

J Virol. 2011 Oct;85(19):10041-7. doi: 10.1128/JVI.05445-11. Epub 2011 Jul 27.

Abstract

Herpes simplex virus 1 (HSV-1) is a ubiquitous human pathogen that enters cells by the receptor-mediated fusion of the viral envelope with a host cell membrane. The envelope glycoprotein gD of HSV must bind to one of its receptors for entry to take place. Recent studies using knockout (KO) mice demonstrated that the gD receptors herpesvirus entry mediator (HVEM) and nectin-1 are the primary entry receptors for HSV-2 in the mouse vagina and brain. Nectin-1 was most crucial for the neuronal spread of HSV-2, particularly in the brain. HVEM was dispensable for infection in these models, but when both HVEM and nectin-1 were absent, infection was completely prevented. We sought to determine the receptor requirements of HSV-1 in an ocular model of infection using knockout mice. Wild-type, HVEM KO, nectin-1 KO, and HVEM/nectin-1 double-KO mice were infected via corneal scarification and monitored for clinical signs of infection and viral replication in various tissues. We report that either HVEM or nectin-1 must be present for HSV-1 infection of the cornea. Additionally, we observed that the infection was attenuated in both HVEM KO and nectin-1 KO mice. This is in contrast to what was reported for studies of HSV-2 in vagina and brain and suggests that receptor requirements for HSV vary depending on the route of inoculation and/or serotype.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cornea / virology*
  • Disease Models, Animal
  • Eye Diseases / pathology
  • Eye Diseases / virology
  • Herpesviridae Infections / pathology
  • Herpesviridae Infections / virology
  • Herpesvirus 1, Human / pathogenicity*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nectins
  • Receptors, Tumor Necrosis Factor, Member 14 / genetics
  • Receptors, Tumor Necrosis Factor, Member 14 / metabolism*
  • Receptors, Virus / genetics
  • Receptors, Virus / metabolism*
  • Rodent Diseases / pathology
  • Rodent Diseases / virology
  • Virus Internalization*

Substances

  • Cell Adhesion Molecules
  • NECTIN1 protein, human
  • Nectin1 protein, mouse
  • Nectins
  • Receptors, Tumor Necrosis Factor, Member 14
  • Receptors, Virus