Herpes virus entry mediator in human corneal epithelial cells modulates the production of inflammatory cytokines in response to HSV type 1 challenge

Ophthalmic Res. 2015;54(3):128-34. doi: 10.1159/000437209. Epub 2015 Sep 1.

Abstract

Aims: To investigate the role of herpes virus entry mediator (HVEM) in viral entry and inflammatory cytokine production in response to herpes simplex virus (HSV) type 1 challenge in human corneal epithelial cells.

Methods: HVEM expression in human corneal epithelial cells was determined by immunofluorescence and flow cytometry. The HSV-1 virus expressing β-galactosidase was used to challenge corneal epithelial cells and viral entry assays were performed to ascertain HSV-1 entry into cells. Levels of cytokines TNF-α, IL-6, IFN-x03B3;, IL-12, and IL-18 and chemokines MIP-1α, MIP-1β and MIP-2 were detected in corneal epithelial cells treated with control or HVEM siRNA in response to HSV-1 challenge.

Results: Human corneal epithelial cells were positive for HVEM expression and showed high susceptibility to HSV-1 entry. Silencing of HVEM did not alter viral entry dramatically. However, levels of the cytokine IFN-x03B3; and chemokines MIP-1α and MIP-1β were measured to be higher in HVEM siRNA-treated cells than control after HSV-1 challenge.

Conclusions: HVEM in human corneal epithelial cells may act to dampen the production of some cytokines and chemokines and thus it may modulate the innate immune response against HSV-1. This may provide a novel mechanism for the pathogenesis of HSV-1 infection in the cornea.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cytokines / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Epithelium, Corneal / metabolism
  • Epithelium, Corneal / virology*
  • Flow Cytometry
  • Fluorescent Antibody Technique, Indirect
  • Gene Silencing / physiology
  • Herpesvirus 1, Human / physiology*
  • Humans
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Receptors, Tumor Necrosis Factor, Member 14 / genetics
  • Receptors, Tumor Necrosis Factor, Member 14 / metabolism*
  • Vero Cells
  • Virus Replication

Substances

  • Cytokines
  • RNA, Small Interfering
  • Receptors, Tumor Necrosis Factor, Member 14