Altered tryptophan metabolism in mice with herpes simplex virus encephalitis: increases in spinal cord quinolinic acid.
Mice infected with the herpes simplex virus, type-1, developed a paralysis which was associated with increased levels of the neurotoxin quinolinic acid (QUIN). The largest increases in QUIN were observed in the spinal cord with much smaller changes in the rostral forebrain or serum. The time course for the paralysis coincided with the increase in spinal cord QUIN, a maximal 40-fold elevation, at 7-10 days post infection. The time course suggested that the increases in QUIN were due to its local synthesis. Consistent with this possibility, herpes virus-infected mice had increased activities of indoleamine 2,3-dioxygenase and kynurenine hydroxylase (two key enzymes in QUIN formation), when compared to non-infected controls. Since QUIN is formed by activated macrophages, these new data are consistent with QUIN formation as part of the host response to a pathogen whose importance is discussed.
Reinhard
J F
JF
Department of Molecular-Pharmacology, Glaxo Wellcome Inc., Research Triangle Park, NC 27709, USA. jfr43211@glaxo.com
D000818:Animals; D001921:Brain / Q000378:metabolism*; D018792:Encephalitis, Viral / Q000378:metabolism*; D006561:Herpes Simplex / Q000378:metabolism*; D018259:Herpesvirus 1, Human; D007737:Kynurenine / Q000378:metabolism; D050601:Kynurenine 3-Monooxygenase; D008297:Male; D051379:Mice; D006899:Mixed Function Oxygenases / Q000378:metabolism; D016548:Prosencephalon / Q000378:metabolism; D017378:Quinolinic Acid / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000378:metabolism
D007737:Kynurenine; D014364:Tryptophan; D006899:Mixed Function Oxygenases; D014366:Tryptophan Oxygenase; D050601:Kynurenine 3-Monooxygenase; D017378:Quinolinic Acid