Oxidative stress and release of bioactive lipid peroxidation by‐products following herpes simplex virus infection of neural cell cultures

Abstract

Herpes simplex virus type 1 (HSV‐1) encephalitis is associated with oxidative tissue damage. The relative contributions of direct viral toxic effects and that of reactive inflammation to this damage are unknown. To determine whether HSV‐1 infection causes oxidative stress and lipid peroxidation in neural cells, mouse P19N neural cell cultures were infected with HSV‐1 and cellular levels of reactive oxygen species (ROS) and the release of lipid peroxidation by‐products malondialdehyde (MDA) and hydroxyalkenals [4‐HAE (predominantly 4‐hydroxy‐2‐nonenal, HNE)] into the tissue culture medium were then measured. HSV‐1 infection increased ROS levels in neural cells as early as one hour post infection (p.i.) and ROS levels remained elevated at 24 hours p.i. HSV‐1 infection also was associated with increased levels of MDA/HAE in the culture medium at 2 and 4 hours p.i. HSV‐1 replication in P19N cells was inhibited by the antioxidant compound ebselen and high concentrations of HNE, but was increased by low concentrations of HNE. These findings suggest that viral effects may directly contribute to oxidative tissue damage caused by HSV‐1 encephalitis. Furthermore, these data suggest that HSV‐1 infection‐induced soluble, bioactive lipid peroxidation by‐products may be mediators of HSV‐1‐induced tissue damage of infected and bystander cells as well as regulators of HSV‐1 replication in the nervous system.