Journal of NeuroVirology

, Volume 13, Issue 5, pp 416–425 | Cite as

Herpes simplex virus type 1 infection induces oxidative stress and the release of bioactive lipid peroxidation by-products in mouse P19N neural cell cultures

  • Jerry H. Kavouras
  • Emese Prandovszky
  • Klara Valyi-Nagy
  • S. Krisztian Kovacs
  • Vaibhav Tiwari
  • Maria Kovacs
  • Deepak Shukla
  • Tibor Valyi-Nagy
Article

Abstract

To determine whether herpes simplex virus type 1 (HSV-1) infection causes oxidative stress and lipid peroxidation in cultured neural cells, mouse P19 embryonal carcinoma cells were differentiated into cells with neural phenotypes (P19N cells) by retinoic acid and were then infected with HSV-1. Cellular levels of reactive oxygen species (ROS) and the release of lipid peroxidation by-products into the tissue culture medium were then measured by the generation of fluorescent markers hydroxyphenyl fluorescein and a stable chromophore produced by lipid peroxidation products, malondialdehyde (MDA) and hydroxyalkenals (4-HAEs; predominantly 4-hydroxy-2-nonenal [HNE]), respectively. HSV-1 infection increased ROS levels in neural cells as early as 1 h post infection (p.i.) and ROS levels remained elevated at 24 h p.i. This viral effect required viral entry and replication as heat- and ultraviolet light-inactivated HSV-1 were ineffective. HSV-1 infection also was associated with increased levels of MDA/HAE in the culture medium at 2 and 4 h p.i., but MDA/HAE levels were not different from those detected in mock infected control cultures at 1, 6, and 24 h p.i. HSV-1 replication in P19N cells was inhibited by the antioxidant compound ebselen and high concentrations of HNE added to the cultures, but was increased by low concentrations of HNE. These findings indicate that HSV-1 infection of neural cells causes oxidative stress that is required for efficient viral replication. Furthermore, these observations raise the possibility that soluble, bioactive lipid peroxidation by-products generated in infected neural cells may be important regulators of HSV-1 pathogenesis in the nervous system.

Keywords

4-hydroxy-2-nonenal HSV-1 lipid peroxidation malondialdehyde oxidative stress neural cell culture 

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Copyright information

© Journal of NeuroVirology, Inc. 2007

Authors and Affiliations

  • Jerry H. Kavouras
    • 1
    • 4
  • Emese Prandovszky
    • 1
  • Klara Valyi-Nagy
    • 1
  • S. Krisztian Kovacs
    • 1
  • Vaibhav Tiwari
    • 2
    • 3
  • Maria Kovacs
    • 2
  • Deepak Shukla
    • 2
    • 3
  • Tibor Valyi-Nagy
    • 1
  1. 1.Department of PathologyUniversity of Illinois at Chicago, College of MedicineChicagoUSA
  2. 2.Department of Ophthalmology and Visual SciencesUniversity of Illinois at Chicago, College of MedicineChicagoUSA
  3. 3.Department of Microbiology and ImmunologyUniversity of Illinois at Chicago, College of MedicineChicagoUSA
  4. 4.Department of BiologyLewis UniversityRomeovilleUSA

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