Teratogenic effects of neonatal arenavirus infection on the developing rat cerebellum are abrogated by passive immunotherapy.
The effects of viral infection on the developing nervous system and the potential of passive immunotherapy to protect against infection were examined. When 4-day-old Lewis rats were injected intracerebrally with lymphocytic choriomeningitis virus (LCMV) the majority of stem cells within the external granular layer of the developing cerebellum became infected. The infection progressed to the molecular layer, internal granular layer, and the Purkinje cells. By 15 days postinfection the molecular and internal granular layers of LCMV-infected cerebella were noticeably thinner than those in the controls and the individual folia were smaller. Neurons remained infected for up to 40 days as determined by immunohistochemistry. However, in rats treated with rat monoclonal anti-LCMV antibodies the staining was limited to the cells of ependyma and choroid plexus and was not detectable by 15 days postinfection. Macroscopically the infection resulted in pronounced hypoplasia, with the cerebella of 21-day-old LCMV-infected rats weighing 52 +/- 10 mg compared with 159 +/- 30 mg for control rats. Antibody-treated rats exhibited normal cerebellar size and development. Neutralizing antibodies specific for the viral GP-1 glycoprotein were protective but nucleoprotein-specific antibodies were not. Furthermore, suckling rat pups born of and nursed by LCMV-immune mothers were spared from cerebellar disease following neonatal infection. These results suggest that passive immunotherapy of neonates can provide effective protection against teratogenic effects of neonatal viral infection on the developing CNS.
Baldridge
J R
JR
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037.
Pearce
B D
BD
Parekh
B S
BS
Buchmeier
M J
MJ
D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000627:therapeutic use*; D000918:Antibody Specificity; D001667:Binding, Competitive; D001921:Brain / Q000196:embryology / Q000382:microbiology; D002531:Cerebellum / Q000002:abnormalities* / Q000196:embryology / Q000382:microbiology; D002831:Choroid Plexus / Q000382:microbiology; D004797:Enzyme-Linked Immunosorbent Assay; D004805:Ependyma / Q000382:microbiology; D005260:Female; D007112:Immunity, Maternally-Acquired; D007150:Immunohistochemistry; D016219:Immunotherapy, Adoptive; D008216:Lymphocytic Choriomeningitis / Q000473:pathology / Q000628:therapy*; D008297:Male; D009474:Neurons / Q000382:microbiology; D009500:Neutralization Tests; D009929:Organ Size; D051381:Rats
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral