SpringerLink
Log in

Herpes simplex virus type 1 encephalitis is associated with elevated levels of F2-isoprostanes and F4-neuroprostanes

  • Published:
Journal of NeuroVirology Aims and scope Submit manuscript

Abstract

To better understand the pathogenesis of herpes simplex virus type 1 (HSV-1) infections of the nervous system, concentrations of F4-neuroprostanes (F4-NP) and F2-isoprostanes (F2-IP) in the murine brain were determined following intracerebral inoculation of HSV-1 or normal saline. F4-NP are highly selective, quantitative markers of neuronal oxidative damage, while F2-IP are markers of oxidative damage to brain tissue not limited to a certain cell type. In contrast to saline-treated control animals, HSV-1-infected animals developed encephalitic symptoms associated with severe inflammation, widespread HSV-1 protein expression, and significantly elevated F4-NP and F2-IP levels in the brain. Survivors of acute HSV-1 infection showed no encephalitic symptoms 2 to 3 weeks following virus inoculation. Brain tissue derived from mice euthanized 2 month after virus inoculation demonstrated expression of HSV-1 latency-associated transcripts without detectable HSV-1 protein expression. However, brain tissue from these animals showed focal chronic inflammation, moderately elevated F2-IP levels, and normal levels of F4-NP. These observations provide novel biochemical evidence that oxidant tissue injury is a mechanism underlying neuronal damage during acute HSV-1 encephalitis and suggest that oxidative damage to tissue may continue in the mammalian brain until at least several weeks after recovery from the symptomatic phase of HSV-1 infection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (France)

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adler H, Beland JL, Del-Pan NC, Kobzik L, Brewer JP, Martin TR, Rimm IJ (1997). Suppression of herpes simplex virus type 1 (HSV-1)-induced pneumonia in mice by inhibition of inducible nitric oxide synthase (iNOS, NOS2). J Exp Med 185: 1533–1540.

    Article  CAS  PubMed  Google Scholar 

  • Akaike T, Suga M, Maeda H (1998). Free radicals in viral pathogenesis: Molecular mechanisms involving superoxide and NO. Proc Soc Ex Biol Med 217: 64–73.

    CAS  Google Scholar 

  • Baringer JR, Pisani P (1994). Herpes simplex virus genomes in human nervous system tissues analyzed by polymerase chain-reaction. Ann Neurol 36: 823–829.

    Article  CAS  PubMed  Google Scholar 

  • Boven LA, Gomes L, Hery C, Gray F, Verhoef J, Portegies P, Tardieu M, Nottet HS (1999). Increased peroxynitrite activity in AIDS dementia complex: Implications for neuropathogenesis of HIV-1 infection. J Immonol 162: 4319–4327.

    CAS  Google Scholar 

  • Cabrera CV, Wohlenberg C, Openshaw H, Rey Mendez M, Puga A, Notkins AL (1980). Herpes simplex virus DNA sequences in the CNS of latently infected mice. Nature 288: 288–290.

    Article  CAS  PubMed  Google Scholar 

  • Cantin EM, Hinton DR, Chen J, Openshaw H (1995). Gamma interferon expression during acute and latent nervous system infection by herpes simplex virus type 1. J Virol 69: 4898–4905.

    CAS  PubMed  Google Scholar 

  • Chen SH, Garber DA, Schaffer PA, Knipe DM, Coen DM (2000). Persistent elevated expression of cytokine transcripts in ganglia latently infected with herpes simplex virus in the absence of ganglionic replication or reactivation. Virology 278: 207–216.

    Article  CAS  PubMed  Google Scholar 

  • Croen D (1993). Evidence for antiviral effect of nitric oxide. Inhibition of herpes simplex virus type 1 replication. J Clin Invest 91: 2446–2452.

    Article  CAS  PubMed  Google Scholar 

  • Daheshia M, Kanangat S, Rouse BT (1998). Production of key molecules by ocular neutrophils early after herpetic infection of the cornea. Exp Eye Res 67: 619–624.

    Article  CAS  PubMed  Google Scholar 

  • Dobson CB, Itzhaki RF (1999). Herpes simplex virus type 1 and Alzheimer’s disease. Neurobiol Aging 20: 457–465.

    Article  CAS  PubMed  Google Scholar 

  • Ellison D, Love S (1996). Acute viral infections. In Neuropathology. Ellison D, Love S (eds). Mosby (Harcourt Publishers Limited): London, pp 12.1–12.19.

    Google Scholar 

  • Feduchi E, Alonso MA, Carrasco L (1989). Human gamma interferon and tumor necrosis factor exert a synergistic blockade on the replication of herpes simplex virus. J Virol 63: 1354–1359.

    CAS  PubMed  Google Scholar 

  • Fraser NW, Lawrence WC, Wroblewska Z, Gilden DH, Koprowski H (1981). Herpes simplex type 1 DNA in human brain tissue. Proc Natl Acad Sci USA 78: 6461–6465.

    Article  CAS  PubMed  Google Scholar 

  • Fujii S, Akaike T, Maeda H (1999). Role of nitric oxide in the pathogenesis of herpes simplex virus encephalitis in rats. Virology 256: 203–212.

    Article  CAS  PubMed  Google Scholar 

  • Fujioka N, Ohashi K, Ikeda M, Kurimoto M (2000). Autocrine intreferon-beta stimulation augments nitric oxide production by mouse macrophage J774A.1 cells infected with herpes simplex virus type 1. Microbiol Immunol 44: 283–287.

    CAS  PubMed  Google Scholar 

  • Geiger DK, Gurushanthaiah D, Howes EL, Lewandowski GA, Reed JC, Bloom FE, Sarvetnick NE (1995). Cytokine-mediated survival from lethal herpes simplex virus infection: Role of programmed neuronal death. Proc Natl Acad Sci USA 92: 3411–3415.

    Article  CAS  PubMed  Google Scholar 

  • Geiger DK, Nash TC, Sawyer S, Krahl T, Patstone G, Reed JC, Krajewski S, Dalton D, Buchmeier MJ, Sarvetnick NE (1997). Interferon-γ protects against herpes simplex virus type 1-mediated neuronal death. Virology 238: 189–197.

    Article  CAS  PubMed  Google Scholar 

  • Halliwell B, Gutteridge JM (1999). Free radicals in biology and medicine. 3rd ed. Oxford Univ Press: Oxford, UK.

    Google Scholar 

  • Itzhaki RF, Lin WR, Shang D, Wilcock GK, Faragher B, Jamieson GA (1997). Herpes simplex virus type 1 in brain and risk of Alzheimer’s disease. Lancet 349: 241–244.

    Article  CAS  PubMed  Google Scholar 

  • Karupiah G, **e QW, Buller RM, Nathan C, Duarte C, MacMicking JD (1993). Inhibition of viral replication by interferon-gamma-induced nitric oxide synthase. Science 261: 1445–1448.

    Article  CAS  PubMed  Google Scholar 

  • Koprowski H, Zheng YM, Heber-Katz E, Fraser N, Rorke L, Fu ZF, Hanlon C, Dietzschold B (1993). In vivo expression of inducible nitric oxide synthetase in experimentally induced neurologic diseases. Proc Natl Acad Sci USA 90: 3024–3027.

    Article  CAS  PubMed  Google Scholar 

  • Liedke W, Opalka B, Zimmermann CW, Lignitz E (1993). Age distribution of latent herpes simplex virus 1 and varicella-zoster virus genome in human nervous tissue. J Neurol Sci 116: 6–11.

    Article  Google Scholar 

  • Lopez-Guerrero JA, Alonso MA (1997). Nitric oxide production induced by herpes simplex virus type 1 does not alter the course of the infection in human monocytic cells. J Gen Virol 78: 1977–1980.

    CAS  PubMed  Google Scholar 

  • MacLean A, Wei XQ, Huang FP, Al-Alem UA, Chan WL, Liew FY (1998). Mice lacking inducible nitric-oxide synthase are more susceptible to herpes simplex virus infection despite enhanced Th1 cell responses. J Gen Virol 79: 825–830.

    CAS  PubMed  Google Scholar 

  • Meyding-Lamade U, Hass J, Lamade W, Stingele K, Kehm R, Fath A, Heinrich K, Storch Hagenlocher B, Wildemann B (1998). Herpes simplex virus encephalitis: Long-term comparative study of viral load and the expression of immunologic nitric-oxide synthetase in mouse brain tissue. Neurosci Lett 244: 9–12.

    Article  CAS  PubMed  Google Scholar 

  • Matthews N, Neale ML, Jackson SK, Stark JM (1987). Tumour cell killing by tumour necrosis factor: Inhibition by anaerobic conditions, free radical scavengers and inhibitors of arachidonate metabolism. Immunology 62: 153–155.

    CAS  PubMed  Google Scholar 

  • Morrow JD, Roberts LJ (1997). The isoprostanes: Unique bioactive products of lipid peroxidation. Prog Lipid Res 36: 1–21.

    Article  CAS  PubMed  Google Scholar 

  • Nucci C, Palamara AT, Ciriolo MR, Nencioni L, Savini P, D’Agostini C, Rotilio G, Cerulli L, Garaci E (2000). Imbalance in corneal redox state during herpes simplex virus 1-induced keratitis in rabbits. Effectiveness of exogenous glutathione supply. Exp Eye Res 70: 215–220.

    Article  CAS  PubMed  Google Scholar 

  • Palu G, Biasolo MA, Sartor G, Masotti L, Papini E, Floreani M, Palatini P (1994). Effects of herpes simplex virus type 1 infection on the plasma membrane and related functions of HeLa S3 cells. J Gen Virol 75: 3337–3344.

    Article  CAS  PubMed  Google Scholar 

  • Patel M, Liang L, Roberts LJ (2001). Enhanced hippocampal F2-isoprostane formation following kainate-induced seizures. J Neurochem 79: 1065–1069.

    Article  CAS  PubMed  Google Scholar 

  • Pelosi E, Rozenberg F, Coen DM, Tyler KL (1998). A herpes simplex virus DNA polymerase mutation that specifically attenuates neurovirulence in mice. Virology 252: 364–372.

    Article  CAS  PubMed  Google Scholar 

  • Peterhans E (1997a). Reactive oxygen species and nitric oxide in viral diseases. Biol Trace Elem Res 56: 107–116.

    Article  CAS  PubMed  Google Scholar 

  • Peterhans E (1997b). Oxidants and antioxidants in viral diseases: Disease mechanisms and metabolic regulation. J Nutri 127: 962S-965S.

    CAS  Google Scholar 

  • Roberts LJ, Montine TJ, Markesbery WR, Tapper AR, Hardy P, Chemtob S, Dettbarn WD, Morrow JD (1998). Formation of isoprostane-like compounds (neuroprostanes) in vivo from docosahexaenoic acid. J Biol Chem 273: 13605–13612.

    Article  CAS  PubMed  Google Scholar 

  • Roizman B, Knipe DM (2001). Herpes simplex viruses and their replication. In Fields’ Virology. Knipe DM, Howley PM (eds). Lippincott-Raven: Philadelphia, pp 2399–2460.

    Google Scholar 

  • Rossol-Voth R, Rossol S, Schut KH, Corridori S, deCian W, Falke D (1991). In vivo protective effect of tumour necrosis factor alpha against experimental infection with herpes simplex virus type 1. J Gen Virol 72: 143–147.

    Article  CAS  PubMed  Google Scholar 

  • Sanchez-Alcazar JA, Schneider E, Martinez MA, Carmona P, Hernandez-Munoz I, Siles E, De La Torre P, Ruiz-Cabello J, Garcia I, Solis-Herruzo JA (2000). Tumor necrosis factor-alpha increases the steady-state reduction of cytochrome b of the mitochondrial respiratory chain in metabolically inhibited L929 cells. J Biol Chem 275: 13353–13361.

    Article  CAS  PubMed  Google Scholar 

  • Schultz P, Arbusow V, Strupp M, Dieterich M, Rauch E, Brandt T (1998). Highly variable distribution of HSV-1-specific DNA in human geniculate, vestibular and spiral ganglia. Neurosci Lett 252: 139–142.

    Article  Google Scholar 

  • Schwarz KB (1996). Oxidative stress during viral infection: A review. Free Radic Biol Med 21: 641–649.

    Article  CAS  PubMed  Google Scholar 

  • Shimeld C, Whiteland JL, Williams NA, Easty DL, Hill TJ (1997). Cytokine production in the nervous system of mice during acute and latent infection with herpes simplex virus type 1. J Gen Virol 78: 3317–3325.

    CAS  PubMed  Google Scholar 

  • Skoldenberg B (1996). Herpes simplex encephalitis. Scan J Infect Dis Suppl 100: 8–13.

    CAS  Google Scholar 

  • Steiner I (1996). Human herpesviruses latent infection in the nervous system. Immunol Rev 152: 157–173.

    Article  CAS  PubMed  Google Scholar 

  • Steiner I, Modor N, Reibstein I, Spivack JG, Fraser NW (1994). Herpes simplex virus type 1 gene expression and reactivation of latent infection in the central nervous system. Neuropathol Appl Neurobiol 20: 253–260.

    Article  CAS  PubMed  Google Scholar 

  • Valyi-Nagy T, Deshmane S, Dillner A, Fraser NW (1991). Induction of cellular transcription factors in trigeminal ganglia of mice by corneal scarification, herpes simplex virus type 1 infection and explantation of trigeminal ganglia. J Virol 65: 4142–4152.

    CAS  PubMed  Google Scholar 

  • Valyi-Nagy T, Deshmane SL, Raengsakulrach B, Nicosia M, Gesser RM, Wysocka M, Dillner A, Fraser NW (1992). Herpes simplex virus type 1 mutant inl814 establishes a unique, slowly progressing infection in SCID mice. J Virol 66: 7336–7345.

    CAS  PubMed  Google Scholar 

  • Valyi-Nagy T, Fareed MU, O’Keefe JS, Gesser RM, MacLean AR, Brown SM, Spivack JG, Fraser NW (1994). An HSV-1 strain 17+ gamma 34.5 deletion mutant 1716 is avirulent in SCID mice. J Gen Virol 75: 2059–2063.

    Article  CAS  PubMed  Google Scholar 

  • Valyi-Nagy T, Olson SJ, Valyi-Nagy K, Montine TJ, Dermody TS (2000). Herpes simplex virus type 1 latency in the murine nervous system is associated with oxidative damage to neurons. Virology 278: 309–321.

    Article  CAS  PubMed  Google Scholar 

  • Valyi-Nagy T, Sidell K, Marnett LJ, Dermody TS, Roberts LJ, Morrow JD, Montine TJ (1999). Divergence of brain prostaglandin H synthetase activity and oxidative damage in mice with encephalitis. J Neuropathol Exp Neurol 58: 1269–1272.

    Article  CAS  PubMed  Google Scholar 

  • Wagner EK, Bloom DC (1997). Experimental investigation of herpes simplex virus latency. Clin Microbiol Rev 10: 419–434.

    CAS  PubMed  Google Scholar 

  • Whitley RJ (2001). Herpes simplex viruses. In Fields’ Virology. Knipe DM, Howley PM (eds). Lippincott-Raven Press: Philadelphia, pp 2461–2510.

    Google Scholar 

  • Wilt SG, Dugger NV, Hitt ND, Hoffman PM (2000). Evidence of oxidative damage in a murine leukemia virus-induced neurodegeneration. J Neurosci Res 62: 440–450.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Tibor Valyi-Nagy

    Present address: Department of Pathology (MC 847), University of Illinois at Chicago, College of Medicine, Room 446, 1819 W. Polk Street, 60612-7335, Chicago, IL, USA

Authors and Affiliations

  1. Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

    Dejan Milatovic, Yueli Zhang, Sandra J. Olson, Kathleen S. Montine, Thomas J. Montine & Tibor Valyi-Nagy

  2. Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

    L. Jackson Roberts & Jason D. Morrow

  3. Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

    L. Jackson Roberts, Jason D. Morrow & Thomas J. Montine

  4. Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

    Terence S. Dermody

  5. Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

    Terence S. Dermody

  6. Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

    Terence S. Dermody & Tibor Valyi-Nagy

Authors
  1. Dejan Milatovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yueli Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sandra J. Olson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kathleen S. Montine
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L. Jackson Roberts
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jason D. Morrow
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Thomas J. Montine
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Terence S. Dermody
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tibor Valyi-Nagy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tibor Valyi-Nagy.

Additional information

This work was supported by Public Health Service awards R01 AG16835 from the National Institute of Aging (TJM), and R01 AI38296 from the National Institute of Allergy and Infectious Diseases (TSD), the Alzheimer’s Disease and Association (TJM), and the Elizabeth B Lamb Center for Pediatric Research (TSD and TVN).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Milatovic, D., Zhang, Y., Olson, S.J. et al. Herpes simplex virus type 1 encephalitis is associated with elevated levels of F2-isoprostanes and F4-neuroprostanes. Journal of NeuroVirology 8, 295–305 (2002). https://doi.org/10.1080/13550280290100743

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1080/13550280290100743

Keywords

Search

Navigation