Abstract
When infection with lymphocytic choriomeningitis (LCMV) occurs during pregnancy, the virus can infect the fetus and injure the fetal brain. However, type, location, and severity of neuropathology differ among cases. One possible explanation for this diversity is that fetuses are infected with different viral strains. Using a rat model of congenital LCMV infection, we investigated how differences in LCMV strain (E350, WE2.2, and Clone 13) affect outcome. Rat pups received intracranial inoculations on postnatal day 4. E350 initially targeted glial cells, while WE2.2 and Clone 13 targeted neurons. The E350 strain induced focal destructive lesions, while the other strains induced global microencephaly. E350 attracted large numbers of CD8+ lymphocytes early in the disease course, while Clone 13 attracted CD4+ lymphocytes, and the infiltration occurred late. The E350 and WE2.2 strains induced large increases in expression of pro-inflammatory cytokines, while Clone 13 did not. The animals infected with E350 and WE2.2 became ataxic and performed poorly on the negative geotaxis assay, while the Clone 13 animals had profound growth failure. Thus, in the developing brain, different LCMV strains have different patterns of infection, neuropathology, immune responses and disease symptoms. In humans, different outcomes from congenital LCMV may reflect infection with different strains.
Highlights
Lymphocytic choriomeningitis virus (LCMV) is a prevalent pathogen that infects large numbers of humans world-wide [1,2,3,4]
This study utilized a neonatal rat model system of congenital LCMV infection to demonstrate that different strains of LCMV have profoundly different biological effects on developing animals in general, and on the developing brain, in particular
Clinical studies examining children with congenital LCMV infection have demonstrated that fetal exposure to LCMV can lead to widely different effects
Summary
Lymphocytic choriomeningitis virus (LCMV) is a prevalent pathogen that infects large numbers of humans world-wide [1,2,3,4]. The viral infection is endemic in wild mice, which secrete the virus in large numbers. Humans can become infected when they contact fomites contaminated with the secretions of infected mice [5,6,7]. LCMV can cross the placenta and infect the developing fetus, where the infection can induce severe and permanent injury [9]. LCMV is strongly neurotropic in the human fetus. The teratogenic effects of congenital LCMV infection are largely confined to the central nervous system, and especially to the brain and retina [10,11,12,13]
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