Journal article
T-Cells Underlie Some but Not All of the Cerebellar Pathology in a Neonatal Rat Model of Congenital Lymphocytic Choriomeningitis Virus Infection
Journal of neuropathology and experimental neurology, Vol.75(11), pp.1031-1047
11/2016
DOI: 10.1093/jnen/nlw079
PMID: 27667772
Abstract
Lymphocytic choriomeningitis virus (LCMV) infection during pregnancy injures the human fetal brain. Neonatal rats inoculated with LCMV are an excellent model of congenital LCMV infection because they develop cerebellar injuries similar to those in humans. To evaluate the role of T-lymphocytes in LCMV-induced cerebellar pathology, congenitally athymic rats, deficient in T-lymphocytes were compared with euthymic rats. Peak viral titers and cellular targets of infection were similar, but viral clearance from astrocytes was impaired in the athymic rats. Cytokines and chemokines rose to higher levels and for a greater duration in the euthymic rats than in their athymic counterparts. The euthymic rats developed an intense lymphocytic infiltration, accompanied by destructive lesions of the cerebellum and a neuronal migration defect because of T-cell-mediated alteration of Bergmann glia. These pathologic changes were absent in the athymic rats but were restored by adoptive transfer of lymphocytes. Athymic rats were not free of pathologic effects, however, as the virus induced cerebellar hypoplasia. Thus, T-lymphocytes play key roles in LCMV clearance, cytokine/chemokine responses, and pathogenesis of destructive lesions and neuronal migration disturbances but not all pathology is T-lymphocyte-dependent. Cerebellar hypoplasia from LCMV occurs even in the absence of T-lymphocytes and is likely due to the viral infection itself.
Details
- Title: Subtitle
- T-Cells Underlie Some but Not All of the Cerebellar Pathology in a Neonatal Rat Model of Congenital Lymphocytic Choriomeningitis Virus Infection
- Creators
- Hannah Klein - From the Department of Neurology (HK, DJB); Department of Pediatrics (GKR, BK); and Neuroscience Graduate Program, University of Iowa College of Medicine, Iowa City, Iowa (HK, DJB)Glenda K Rabe - From the Department of Neurology (HK, DJB); Department of Pediatrics (GKR, BK); and Neuroscience Graduate Program, University of Iowa College of Medicine, Iowa City, Iowa (HK, DJB)Bahri Karacay - From the Department of Neurology (HK, DJB); Department of Pediatrics (GKR, BK); and Neuroscience Graduate Program, University of Iowa College of Medicine, Iowa City, Iowa (HK, DJB)Daniel J Bonthius - From the Department of Neurology (HK, DJB); Department of Pediatrics (GKR, BK); and Neuroscience Graduate Program, University of Iowa College of Medicine, Iowa City, Iowa (HK, DJB)
- Resource Type
- Journal article
- Publication Details
- Journal of neuropathology and experimental neurology, Vol.75(11), pp.1031-1047
- DOI
- 10.1093/jnen/nlw079
- PMID
- 27667772
- NLM abbreviation
- J Neuropathol Exp Neurol
- ISSN
- 0022-3069
- eISSN
- 1554-6578
- Publisher
- Oxford University Press
- Language
- English
- Date published
- 11/2016
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neonatology
- Record Identifier
- 9984065737802771
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