Herpes simplex virus 1 infection induces the expression of proinflammatory cytokines, interferons and TLR7 in human corneal epithelial cells

Immunology. 2006 Feb;117(2):167-76. doi: 10.1111/j.1365-2567.2005.02275.x.


Herpetic epithelial and stromal keratitis is a sight-threatening ocular infection. To study the role of the epithelium in the innate response to herpes simplex virus 1 (HSV-1) infection of the cornea, we used a telomerase-immortalized human corneal epithelial cell (HCEC) line, HUCL, and primary HCECs as a model and infected the cells with HSV-1 (KOS strain). HSV-1 infection of HCECs resulted in a two-phase activation of nuclear factor-kappaB (NF-kappaB), JNK and p38, with the first peak at 1-4 hr and a second peak at 8 hr. Concomitant with the first peak of activation, transcriptional expression of interleukin (IL)-6, IL-8, tumour necrosis factor (TNF)-alpha and interferon (IFN)-beta was rapidly induced in HSV-1-infected cells. HSV-1 infection also induced the production of IL-6, IL-8, and TNF-alpha in both HUCL cells and primary HCECs. Coincident with the second phase of NF-kappaB activation in HSV-1-infected HCECs, the expression of Toll-like receptor 7 (TLR7) was induced, whereas the level of TLR3 was greatly down-regulated. Thus, in response to HSV-1 infection, HCECs produce proinflammatory cytokines, leading to infiltration, and IFNs to enhance the antiviral activity in the cornea, probably through sequential activation of TLRs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • Epithelium, Corneal / immunology*
  • Gene Expression
  • Herpesvirus 1, Human*
  • Humans
  • Interferons / biosynthesis
  • Interferons / genetics
  • Keratitis, Herpetic / immunology*
  • NF-kappa B / metabolism
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Toll-Like Receptor 7 / biosynthesis*


  • Cytokines
  • NF-kappa B
  • RNA, Messenger
  • TLR7 protein, human
  • Toll-Like Receptor 7
  • Interferons