5-aminolaevulinic acid and photodynamic therapy reduce HSV-1 replication in HaCat cells through an apoptosis-independent mechanism

Photodermatol Photoimmunol Photomed. 2008 Oct;24(5):237-43. doi: 10.1111/j.1600-0781.2008.00367.x.

Abstract

Background: Photodynamic therapy (PDT) involves the use of a photosensitizing agent, which may require metabolic synthesis (i.e. a prodrug), followed by light activation. Numerous studies have advanced PDT as a means for treating bacteria, fungi and viruses. In this study, the photoinactivation of Herpes simplex virus type 1 (HSV-1) in human keratinocytes using 5-aminolaevulinic acid (5-ALA) was investigated.

Methods: HaCat cells were infected with HSV-1 and treated with 5-ALA to verify its antiviral effect during the stages of adsorption and penetration to host cells. Immunoblot analysis was used to estimate the effect of ALA-PDT on the production of viral proteins glycoprotein D (gD), infected cell proteins (ICP) 27 and virion protein (VP) 16. We also investigated whether the effect of ALA-PDT was associated with a cellular apoptotic mechanism through DNA fragmentation and the study of p53, PARP and caspase-3 protein expression.

Results: While the treatment of ALA-PDT after the viral adsorption period reduced HSV-1 replication by about 70%, it did not act on the virus in the first phase of infection. The viral proteins' expressions were reduced by ALA-PDT treatments. There was no evidence of ALA-PDT-induced apoptosis.

Conclusion: Our data suggest that the target of photoinactivation appears to be viral replication and not a cellular response.

MeSH terms

  • Aminolevulinic Acid / pharmacology*
  • Aminolevulinic Acid / therapeutic use
  • Apoptosis / drug effects*
  • Apoptosis / radiation effects
  • Cell Line
  • Gene Expression Regulation, Viral / drug effects
  • Gene Expression Regulation, Viral / radiation effects
  • Herpes Simplex / drug therapy*
  • Herpes Simplex / metabolism
  • Herpesvirus 1, Human / metabolism*
  • Humans
  • Keratinocytes / virology
  • Photochemotherapy*
  • Photosensitizing Agents / pharmacology*
  • Photosensitizing Agents / therapeutic use
  • Prodrugs / pharmacology*
  • Prodrugs / therapeutic use
  • Viral Proteins / biosynthesis
  • Virus Replication / drug effects*
  • Virus Replication / radiation effects

Substances

  • Photosensitizing Agents
  • Prodrugs
  • Viral Proteins
  • Aminolevulinic Acid