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

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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.

Keywords: 5-aminolaevulinic acid; HSV-1; HaCat cells; photodynamic therapy

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1600-0781.2008.00367.x

Affiliations: 1: National Cancer Institute of Naples “G. Pascale”, Naples, Italy, and 2: Department of Experimental Medicine, Microbiology and Clinical Microbiology Section, Faculty of Medicine and Surgery, Second University of Naples, Naples, Italy

Publication date: October 1, 2008

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