View More View Less
  • 1 Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Hospital Jerusalem, Israel
  • | 2 Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Hospital Jerusalem, Israel
  • | 3 Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Hospital Jerusalem, Israel
Restricted access

Purchase article

USD  $25.00

1 year subscription (Individual Only)

USD  $784.00

Experimental models that mimic the clinical syndrome of human viral encephalitis and represent HSV-1 neurotropism were utilized to investigate neuro-pharmacologic changes mediating clinical and behavioral manifestations of encephalitic infection of the central nervous system with HSV-1-induced rapid activation of the hypothalamic - pituitary - adrenocortical (HPA) axis and production of brain derived interleukin-1 (IL-1) and prostaglandin E2 (PG-E2), independently of viral replication. HSV-1 infection induced clinical signs of fever, motor hyperactivity and aggressive behavior. These manifestations were dependent on a permissive action of circulating glucocorticoids and not related to the degree of viral replication in the brain. Hyperthermia and HPA axis activation were also specifically dependent on HSV-1-induced brain IL-1 and PG-E2. The chronic neurological sequel or fatal outcome of HSV-1 encephalitis may be due to viral replication and brain tissue destruction, which are dependent on virus encoded virulence genes. In contrast, the clinical and behavioral signs in the acute phase are a result of activation of neurochemical systems, including cytokines, prostaglandinds and catecholamines. Circulating glucocorticoids play an essential role in mediating the physiologic actions of HSV-1-induced brain products and the clinical syndrome of encephalitis.

  • Becker, Y., Hadar, J., Tabor, E., Ben-Hur, T., Raibstein, I., Rosen, A., et al.: A sequence in HpaI-P fragment of herpes simplex virus-1 DNA determines intraperitoneal virulence in mice. Virology 149, 255-259 (1986).

    'et al.: A sequence in HpaI-P fragment of herpes simplex virus-1 DNA determines intraperitoneal virulence in mice. ' () 149 Virology : 255 -259.

    • Search Google Scholar
  • Ben-Hur, T., Rosenthal, J., Itzik, A., Weidenfeld, J.: Adrenocortical activation by herpes virus: involvement of IL-1 beta and central noradrenergic system. Neuroreport 7, 927-931 (1996).

    'Adrenocortical activation by herpes virus: involvement of IL-1 beta and central noradrenergic system. ' () 7 Neuroreport : 927 -931.

    • Search Google Scholar
  • Ben-Hur, T., Asher, Y., Tabor, E., Darai, G., Becker, Y.: HSV-1 virulence for mice by the intracerebral route is encoded by the BamHI-L DNA fragment containing the cell fusion gene. Arch Virol 96, 117-122 (1987).

    'HSV-1 virulence for mice by the intracerebral route is encoded by the BamHI-L DNA fragment containing the cell fusion gene. ' () 96 Arch Virol : 117 -122.

    • Search Google Scholar
  • Ben-Hur, T., Conforti, N., Itzik, A., Weidenfeld, J.: Effects of HSV-1, a neurotropic virus, on the hypothalamic-pituitary-adrenocortical axis in rats. Brain Res 702, 17-22 (1995).

    'Effects of HSV-1, a neurotropic virus, on the hypothalamic-pituitary-adrenocortical axis in rats. ' () 702 Brain Res : 17 -22.

    • Search Google Scholar
  • Ben-Hur, T., Rosenthal, J., Itzik, A., Weidenfeld, J.: Rescue of HSV-1 neurovirulence is associated with induction of brain interleukin-1 expression, prostaglandin synthesis and neuroendocrine responses. J Neurovirol 2, 279-288 (1996).

    'Rescue of HSV-1 neurovirulence is associated with induction of brain interleukin-1 expression, prostaglandin synthesis and neuroendocrine responses. ' () 2 J Neurovirol : 279 -288.

    • Search Google Scholar
  • Ben-Hur, T., Rosen-Wolff, A., Lamade, W., Darai, G., Becker, Y.: HSV-1 DNA sequence determining intraperitoneal pathogenicity in mice is required for transcription of viral immediate-early genes in macrophages. Virology 163, 397-404 (1988).

    'HSV-1 DNA sequence determining intraperitoneal pathogenicity in mice is required for transcription of viral immediate-early genes in macrophages. ' () 163 Virology : 397 -404.

    • Search Google Scholar
  • Ben-Hur, T. C. R., Itzik, A., Yirmiya, R., Weidenfeld, J.: The acute effects of purified and UV-inactivated HSV-1 on the hypothalamic-pituitary-adrenocortical axis. Neuroendocrinology 74, 160-166 (2001).

    'The acute effects of purified and UV-inactivated HSV-1 on the hypothalamic-pituitary-adrenocortical axis. ' () 74 Neuroendocrinology : 160 -166.

    • Search Google Scholar
  • Ben-Hur, T. C. R., Itzik, A., Barak, O., Yirmiya, R., Weidenfeld, J.: A novel permissive role for glucocorticoids in induction of febrile and behavioral signs of experimental herpes simplex virus encephalitis. Neuroscience 108, 119-127 (2001).

    'A novel permissive role for glucocorticoids in induction of febrile and behavioral signs of experimental herpes simplex virus encephalitis. ' () 108 Neuroscience : 119 -127.

    • Search Google Scholar
  • Chou, J., Kern, E. R., Whitley, R. J., Roizman, B.: Mapping of herpes simplex virus-1 neurovirulence to gamma 134.5, a gene nonessential for growth in culture. Science 250, 1262-1266 (1990).

    'Mapping of herpes simplex virus-1 neurovirulence to gamma 134.5, a gene nonessential for growth in culture. ' () 250 Science : 1262 -1266.

    • Search Google Scholar
  • Chou, J., Roizman, B.: The gamma 1(34.5) gene of herpes simplex virus 1 precludes neuro-blastoma cells from triggering total shutoff of protein synthesis characteristic of programed cell death in neuronal cells. Proc Natl Acad Sci USA 89, 3266-3270 (1992).

    'The gamma 1(34.5) gene of herpes simplex virus 1 precludes neuro-blastoma cells from triggering total shutoff of protein synthesis characteristic of programed cell death in neuronal cells. ' () 89 Proc Natl Acad Sci USA : 3266 -3270.

    • Search Google Scholar
  • Dingwell, K. S., Doering, L. C., Johnson, D. C.: Glycoproteins E and I facilitate neuron-to-neuron spread of herpes simplex virus. J Virol 69, 7087-7098 (1995).

    'Glycoproteins E and I facilitate neuron-to-neuron spread of herpes simplex virus. ' () 69 J Virol : 7087 -7098.

    • Search Google Scholar
  • Feldman, S., Weidenfeld, J.: Neural mechanisms involved in the corticosteroid feedback effects on the hypothalamo-pituitary-adrenocortical axis. Prog Neurobiol 45, 129-141 (1995).

    'Neural mechanisms involved in the corticosteroid feedback effects on the hypothalamo-pituitary-adrenocortical axis. ' () 45 Prog Neurobiol : 129 -141.

    • Search Google Scholar
  • Goldsmith, K., Chen, W., Johnson, D. C., Hendricks, R. L.: Infected cell protein (ICP)47 enhances herpes simplex virus neurovirulence by blocking the CD8+ T cell response. J Exp Med 187, 341-348 (1998).

    'Infected cell protein (ICP)47 enhances herpes simplex virus neurovirulence by blocking the CD8+ T cell response. ' () 187 J Exp Med : 341 -348.

    • Search Google Scholar
  • Munck, A., Naray-Fejes-Toth, A.: Glucocorticoids and stress: permissive and suppressive actions. Ann NY Acad Sci 746, 115-133 (1994).

    'Glucocorticoids and stress: permissive and suppressive actions. ' () 746 Ann NY Acad Sci : 115 -133.

    • Search Google Scholar
  • Rivier, C., Chizzonite, R., Vale, W.: In the mouse the activation of the hypothalamic-pituitary-adrenal axis by a lipopolysaccharide (endotoxin) is mediated through interleukin-1. Endocrinology 125, 2800-2805 (1989).

    'In the mouse the activation of the hypothalamic-pituitary-adrenal axis by a lipopolysaccharide (endotoxin) is mediated through interleukin-1. ' () 125 Endocrinology : 2800 -2805.

    • Search Google Scholar
  • Rivier, C., Vale, W., Brown, M.: In the rat interleukin-1 alpha and -beta stimulate adreno-corticotropin and catecholamine release. Endocrinology 125, 3096-3102 (1989).

    'In the rat interleukin-1 alpha and -beta stimulate adreno-corticotropin and catecholamine release. ' () 125 Endocrinology : 3096 -3102.

    • Search Google Scholar
  • Saldanha, C. E., Lubinski, J., Martin, C., Nagashunmugam, T., Wang, L., van der Keyl, H. et al.: Herpes simplex virus type 1 glycoprotein E domains involved in virus spread and disease. J Virol 74, 6712-6719 (2000).

    'van der Keyl, H. et al.: Herpes simplex virus type 1 glycoprotein E domains involved in virus spread and disease. ' () 74 J Virol : 6712 -6719.

    • Search Google Scholar
  • Tanimura, S. M., Watts, A. G.: Adrenalectomy dramatically modifies the dynamics of neuropeptide and c-fos gene responses to stress in the hypothalamic paraventricular nucleus. J Neuroendocrinol 12, 715-722 (2000).

    'Adrenalectomy dramatically modifies the dynamics of neuropeptide and c-fos gene responses to stress in the hypothalamic paraventricular nucleus. ' () 12 J Neuroendocrinol : 715 -722.

    • Search Google Scholar
  • Thompson, R. L., Devi-Rao, G. V., Stevens, J. G., Wagner, E. K.: Rescue of a herpes simplex virus type 1 neurovirulence function with a cloned DNA fragment. J Virol 55, 504-508 (1985).

    'Rescue of a herpes simplex virus type 1 neurovirulence function with a cloned DNA fragment. ' () 55 J Virol : 504 -508.

    • Search Google Scholar
  • Tilders, F. J., DeRijk, R. H., Van Dam, A. M., Vincent, V. A., Schotanus, K., Persoons, J. H.: Activation of the hypothalamus-pituitary-adrenal axis by bacterial endotoxins: routes and intermediate signals. Psychoneuroendocrinology 19, 209-232 (1994).

    'Activation of the hypothalamus-pituitary-adrenal axis by bacterial endotoxins: routes and intermediate signals. ' () 19 Psychoneuroendocrinology : 209 -232.

    • Search Google Scholar
  • Weidenfeld, J., Abramsky, O., Ovadia, H.: Effect of interleukin-1 on ACTH and corticosterone secretion in dexamethasone and adrenalectomized pretreated male rats. Neuroendocrinology 50, 650-654 (1989).

    'Effect of interleukin-1 on ACTH and corticosterone secretion in dexamethasone and adrenalectomized pretreated male rats. ' () 50 Neuroendocrinology : 650 -654.

    • Search Google Scholar
  • Weidenfeld, J., Feldman, S.: Effects of adrenalectomy and corticosterone replacement on the hypothalamic-pituitary response to neural stimuli. Brain Res 877, 73-78 (2000).

    'Effects of adrenalectomy and corticosterone replacement on the hypothalamic-pituitary response to neural stimuli. ' () 877 Brain Res : 73 -78.

    • Search Google Scholar
  • Weidenfeld, J., Siegel, R. A., Conforti, N., Chowers, I.: ACTH and corticosterone secretion following indomethacin, in intact, adrenalectomized and dexamethasone-pretreated male rats. Neuroendocrinology 36, 49-52 (1983).

    'ACTH and corticosterone secretion following indomethacin, in intact, adrenalectomized and dexamethasone-pretreated male rats. ' () 36 Neuroendocrinology : 49 -52.

    • Search Google Scholar
  • Whitnall, M. H.: Regulation of the hypothalamic corticotropin-releasing hormone neuro-secretory system. Prog Neurobiol 40, 573-629 (1993).

    'Regulation of the hypothalamic corticotropin-releasing hormone neuro-secretory system. ' () 40 Prog Neurobiol : 573 -629.

    • Search Google Scholar
All Time Past Year Past 30 Days
Abstract Views 90 90 25
Full Text Views 7 1 0
PDF Downloads 1 0 0