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Open AccessArticle

Viral Strain Determines Disease Symptoms, Pathology, and Immune Response in Neonatal Rats with Lymphocytic Choriomeningitis Virus Infection

by Jeffrey M. Plume 1,†, Dylan Todd 1,† and Daniel J. Bonthius 1,2,3,*
1
Neuroscience Program, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
2
Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
3
Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Viruses 2019, 11(6), 552; https://doi.org/10.3390/v11060552
Received: 28 May 2019 / Revised: 11 June 2019 / Accepted: 12 June 2019 / Published: 14 June 2019
(This article belongs to the Special Issue LCMV – A Pillar for Immunology Research)
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. View Full-Text
Keywords: cytokines; behavior; encephalomalacia; microcephaly; astrocytes; Bergman glia; olfaction; cerebellum cytokines; behavior; encephalomalacia; microcephaly; astrocytes; Bergman glia; olfaction; cerebellum
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Plume, J.M.; Todd, D.; Bonthius, D.J. Viral Strain Determines Disease Symptoms, Pathology, and Immune Response in Neonatal Rats with Lymphocytic Choriomeningitis Virus Infection. Viruses 2019, 11, 552.

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