5-aminolaevulinic acid and photodynamic therapy reduce HSV-1 replication in HaCat cells through an apoptosis-independent mechanism.
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.
Ayala
Fabrizio
F
National Cancer Institute of Naples G. Pascale, Naples, Italy.
Grimaldi
Elena
E
Perfetto
Brunella
B
Donnarumma
Maria
M
De Filippis
Anna
A
Donnarumma
Giovanna
G
Tufano
Maria Antonietta
MA
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
D017319:Photosensitizing Agents; D011355:Prodrugs; D014764:Viral Proteins; D000622:Aminolevulinic Acid