Nectin-1-specific entry of herpes simplex virus 1 is sufficient for infection of the cornea and viral spread to the trigeminal ganglia

Mol Vis. 2012:18:2711-6. Epub 2012 Nov 16.

Abstract

Purpose: Primary and recurrent infections of the cornea by herpes simplex virus 1 (HSV-1) are important causes of eye disease. Three unrelated classes of glycoprotein D receptors for HSV-1 entry into cells have been identified. This study was undertaken to uncover the relative significance of nectin-1 as an entry receptor in corneal infection and HSV-1 spread to the trigeminal ganglia (TG), a site important for HSV-1 latency and recurrent corneal infection.

Methods: To assess the significance of nectin-1, a member of the immunoglobulin superfamily, in primary HSV-1 infection and spread to the TG, we used a murine model of corneal infection and a HSV-1 mutant, KOS(Rid1), which can only use nectin-1 for entry. Immunohistochemistry, real-time PCR, and plaque assays using HSV-1 infected tissues were performed.

Results: We demonstrated that receptor usage by HSV-1 limited to nectin-1 does not significantly change the spread of HSV-1 in the corneal epithelium during primary infection. We also found that nectin-1-specific entry does not affect the capacity of the virus to spread to the TG from the cornea.

Conclusions: Our findings suggest that nectin-1 alone is sufficient for HSV-1 entry into the cornea and spread to the TG.

MeSH terms

  • Animals
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Disease Models, Animal
  • Epithelium, Corneal / metabolism*
  • Epithelium, Corneal / pathology
  • Epithelium, Corneal / virology
  • Gene Expression
  • Herpes Simplex / metabolism*
  • Herpes Simplex / pathology
  • Herpes Simplex / virology
  • Herpesvirus 1, Human / genetics
  • Herpesvirus 1, Human / metabolism*
  • Humans
  • Immunohistochemistry
  • Keratitis, Herpetic
  • Mice
  • Mice, Inbred BALB C
  • Mutation
  • Nectins
  • Real-Time Polymerase Chain Reaction
  • Receptors, Virus / genetics
  • Receptors, Virus / metabolism*
  • Trigeminal Ganglion / metabolism*
  • Trigeminal Ganglion / pathology
  • Trigeminal Ganglion / virology
  • Viral Plaque Assay
  • Virus Internalization*
  • Virus Latency
  • Virus Replication

Substances

  • Cell Adhesion Molecules
  • NECTIN1 protein, human
  • Nectin1 protein, mouse
  • Nectins
  • Receptors, Virus