Neuropathology of herpes simplex virus encephalitis in a rat seizure model.
Herpes simplex virus type 1 (HSV-1) is the cause of a serious and often fatal encephalitis. Patients who survive herpes simplex encephalitis (HSE) experience behavioral abnormalities including profound cognitive dysfunctions. We have developed a rat model of acute HSE to investigate the cognitive impairments caused by HSV-1 central nervous system (CNS) infection. Following intranasal inoculation of Lewis rats with a neurovirulent strain of HSV-1, animals shed virus in both ocular and nasal secretions and developed clinical signs of infection, including partial complex motor seizures that eventually generalized. Homogenization assays demonstrated infectious virus in the trigeminal ganglia, olfactory bulbs, and the piriform and entorhinal cortices. Histopathological assessment revealed inflammatory and hemorrhagic lesions in the trigeminal ganglia, olfactory bulbs, amygdala, hippocampus, the piriform and entorhinal cortices, and the spinal trigeminal nuclei. Viral antigens and nucleic acids were also detected within these structures by immunofluorescence microscopy and in situ hybridization, respectively. Viral-induced astrocytic hypertrophy in the CNS was demonstrated by glial fibrillary acidic protein immunoreactivity. Together, these results indicate that HSV-1 has the ability to invade, replicate, and induce site-specific CNS damage in the Lewis rat.
Department of Veteran Affairs Medical Centers, Houston, Texas.
D R
DR
Beers
J S
JS
Henkel
D C
DC
Schaefer
J W
JW
Rose
W G
WG
Stroop
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D002540:Cerebral Cortex / Q000382:microbiology; D004279:DNA, Viral / Q000032:analysis; D004195:Disease Models, Animal; D004660:Encephalitis / Q000235:genetics / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D005260:Female; D017403:In Situ Hybridization; D009830:Olfactory Bulb / Q000382:microbiology; D012367:RNA, Viral / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew / Q000382:microbiology*; D018139:Simplexvirus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D012668:Trigeminal Ganglion / Q000382:microbiology
D000956:Antigens, Viral; D004279:DNA, Viral; D012367:RNA, Viral