title: 5-aminolaevulinic acid and photodynamic therapy reduce HSV-1 replication in HaCat cells through an apoptosis-independent mechanism.
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.
  
  
  CONCLUSIONS
  Our data suggest that the target of photoinactivation appears to be viral replication and not a cellular response.
authors.affiliation: National Cancer Institute of Naples G. Pascale, Naples, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Ayala
authors.forename: Elena
authors.initials: E
authors.lastname: Grimaldi
authors.forename: Brunella
authors.initials: B
authors.lastname: Perfetto
authors.forename: Maria
authors.initials: M
authors.lastname: Donnarumma
authors.forename: Anna
authors.initials: A
authors.lastname: De Filippis
authors.forename: Giovanna
authors.initials: G
authors.lastname: Donnarumma
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Tufano
mesh_terms: D000622:Aminolevulinic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D002460:Cell Line; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000528:radiation effects; D006561:Herpes Simplex / Q000188:drug therapy* / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000821:virology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011355:Prodrugs / Q000494:pharmacology* / Q000627:therapeutic use; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects* / Q000528:radiation effects
chemical_list: D017319:Photosensitizing Agents; D011355:Prodrugs; D014764:Viral Proteins; D000622:Aminolevulinic Acid