Effect of stigmastane derivatives on herpes simplex virus type 1 replication and apoptosis in neurons

PETRERA, E.; NÍTTOLO, A.G.; ALCHÉ, L.E.

Mendoza

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2012

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

The stigmastane derivatives (22S,23S)-22,23-dihydroxystigmast-4-en-3-one (1) and (22S,23S)-3-bromo-5,22,23-trihydroxystigmastan- 6-one(2) prevent Herpes Simplex Virus type 1 (HSV-1) multiplication in vitro and reduce the incidence of herpetic stromal keratitis in a murine model of corneal infection. Considering that at least 90% of the population is infected with HSV-1 and the primary site of virus latency is sensory neurons, we decided to investigate the antiviral effect of both compounds in neuronal cells and also its involvement on cell apoptosis. Three different cellular lines (PC-12, Neuro-2a and SH-SY5Y) were infected with strains KOS and KOS Cgal+ of HSV-1 and then treated with compounds 1 and 2 under no cytotoxic concentrations. The results obtained by plaque assay and stain in situ for -gal activity show that the compounds inhibit up to 99% the replication of both strains of HSV-1 in all cellular lines tested. On the other hand, the study of apoptosis by flow cytometry produced encouraging results. Cell treatment with both compounds under cytotoxic concentration as well as HSV-1 infection induced neuronal apoptosis. Despite of this, the addition of compounds 1 and 2 to the infected cells diminished cell death by apoptosis. We report here that compound 1 and 2 not only have antiherpetic properties but also exert an anti-apoptotic effect in neurons infected with HSV-1.