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

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.

How Bank Vole-PUUV Interactions Influence the Eco-Evolutionary Processes Driving Nephropathia Epidemica Epidemiology—An Experimental and Genomic Approach

“…Only limited conclusions could be reached from these experiments, in particular because bank vole immunogenetic polymorphism [ 20 ] or PUUV genetic diversity [ 13 ] have previously been shown to influence the variability of bank vole/PUUV interaction outcomes. Similar results corroborating the influence of viral diversity were also observed for other viruses, with different strains leading to different patterns of infection (classical swine fever virus (CSFV), [ 32 ]), of immune responses (Lymphocytic Choriomeningitis Virus, [ 33 ]) or excretion dynamics (CSFV, [ 34 ]).…”

Echoencephalography of encephalopathy due to congenital lymphocytic choriomeningitis virus

“…In the human fetus, the presence and function of T‐lymphocytes change with development 33 . In the early pregnancy, when T‐cell function is immature, 34 cerebellar hypoplasia is due to reduced granular cell production, in part due to the effect of TNF produced by astrocytes in response to LCMV infection 9 . T‐lymphocytes are necessary for the generation of destructive lesions and clearance of the virus from the nervous system.…”

“…A different strain of LCMV may produce a less robust T-cell immune response, perhaps explaining why some humans with congenital LCMV infection only have forebrain hypoplasia. 9,34 LCMV intrauterine infection can produce four distinct echoencephalographic images, depending on the timing of maternal infection. 20 First, if maternal infection with LCMV occurs during radial migration of primitive granular cells from their subpial molecular layer location in the cerebellum, 35 As a result, LCMV infection between 18 and 24 weeks causes cerebral hypoplasia with ventriculomegaly, pachygyria, and abnormal opercularization of the insula.…”

“…T‐lymphocytes are necessary for the generation of destructive lesions and clearance of the virus from the nervous system. A different strain of LCMV may produce a less robust T‐cell immune response, perhaps explaining why some humans with congenital LCMV infection only have forebrain hypoplasia 9,34 …”

Micro-Actuated Tunable Hierarchical Silver Nanostructures to Measure Tensile Force for Biomedical Wearable Sensing Applications

“…A number of disorders, such as glaucoma, repetitive strain injury (RSI), cardiomyopathy, axonal injury, etc., which suffer from a limited understanding of their pathophysiology due to the lack of sensors for measuring required data, could benefit tremendously from flexible sensing techniques. The potential causes of these disorders are closely related to continuously applied strains in joints, ligaments, and muscles that hold the internal organs [ 11 , 12 , 13 , 14 , 15 , 16 , 17 ]; hence, monitoring the changes of tension forces in real time via flexible sensors could provide much needed data on these strains. Nevertheless, current flexible sensors are not suitable for directly and accurately monitoring such tension forces.…”