A novel apoptotic interaction between HSV-1 and human corneal epithelial cells

Curr Eye Res. 2003 Mar-Apr;26(3-4):165-74. doi: 10.1076/ceyr.26.3.165.14899.

Abstract

Purpose: Herpes simplex virus type 1 (HSV-1) infects the cornea possibly causing blindness. The specific mechanisms of herpetic keratitis are unclear. We aimed to investigate whether HSV-1 would up- or down-regulate the apoptotic pathway of human corneal epithelial (HCE) cells.

Methods: HSV-1 infection of HCE and Vero cells was demonstrated (immunofluorescence) and apoptotic gene expression was quantified (ribonuclease protection assay). Caspase 8 protein activity (colorimetric assay) was quantified and compared to caspase 8 mRNA amounts from RPA experiments. The apoptotic index of HSV-1 infected HCE and Vero cells (apoptotic index = % of apoptotic cells in infected samples/mock treated samples) was obtained and compared to gene expression.

Results: A down-regulation in apoptotic gene expression was observed in HSV-1 infected HCE cells in contrast to Vero cells (infected and mock treated). Caspase 8 protein levels mirrored caspase 8 mRNA levels in HSV-1 infected HCE cells. The apoptotic index also supports this down-regulation. HSV-1 infected human corneal epithelial cells and Vero cells at similar rates.

Conclusion: HSV-1 down-regulates the apoptotic pathway of human corneal epithelial cells. This down-regulation of apoptotic gene expression seems to be cell specific. Also infectivity is excluded in playing a role in regulation of the apoptotic pathway because HSV-1 replicated at similar rates in HCE and Vero cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis* / genetics
  • Caspase 8
  • Caspase 9
  • Caspases / genetics
  • Caspases / metabolism
  • Cell Line, Transformed
  • Chlorocebus aethiops
  • Down-Regulation
  • Epithelium, Corneal / pathology
  • Epithelium, Corneal / physiopathology*
  • Gene Expression
  • Herpesvirus 1, Human*
  • Humans
  • Keratitis, Herpetic / pathology
  • Keratitis, Herpetic / physiopathology*
  • RNA, Messenger / metabolism
  • Time Factors
  • Vero Cells

Substances

  • RNA, Messenger
  • CASP8 protein, human
  • CASP9 protein, human
  • Caspase 8
  • Caspase 9
  • Caspases