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 paral ysis which was associated with increased levels of the neurotoxin quin olinic acid (QUIN). The largest increases in QUIN were observed in the spinal cord with much smaller changes in the rostral forebrain or ser um. The time course for the paralysis coincided with the increase in s pinal cord QUIN, a maximal 40-fold elevation, al 7-10 days post infect ion. The time course suggested that the increases in QUIN were due to its local synthesis. Consistent with this possibility, herpes virus-in fected mice had increased activities of indoleamine 2,3-dioxygenase an d kynurenine hydroxylase (two key enzymes in QUIN formation), when com pared to non-infected controls. Since QUIN is formed by activated macr ophages, these new data are consistent with QUIN formation as part of the host response to a pathogen whose importance is discussed.