Prevalence and Risk Factors for Lymphocytic Choriomeningitis Virus Infection in Continental Croatian Regions

Lymphocytic choriomeningitis virus (LCMV) is a neglected human pathogen associated with aseptic meningitis, severe systemic infections in immunocompromised persons, and congenital anomalies. Data on the prevalence of LCMV infections are scarce. We analyzed the seroprevalence of LCMV in continental Croatian regions. A total of 338 serum samples of professionally exposed (forestry workers, hunters, agriculture workers in contact with rodents) and non-exposed populations (general population, pregnant women) were tested for the presence of LCMV antibodies using indirect immunofluorescence assay. No participants reported recent febrile disease. LCMV IgG antibodies were detected in 23/6.8% of participants: 9.8% exposed persons and 5.1% non-exposed persons (6.1% in the general population and 3.9% in pregnant women). No participants were LCMV IgM positive. Although higher seropositivity was found in males compared to females (8.9% vs. 4.7%), inhabitants of suburban/rural areas compared to inhabitants of urban areas (9.2% vs. 4.6%), and persons who used well as a source of water compared to those who used tap (11.4% vs. 5.6%), these differences did not reach statistical significance. Results of logistic regression showed that the presence of rodents in the house/yard and cleaning rodent nests were associated with an elevated risk for LCMV infection (OR = 2.962, 95% CI = 1.019–8.607).

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

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.

Lymphocytic Choriomeningitis Virus Infection Demonstrates Higher Replicative Capacity and Decreased Antiviral Response in the First-Trimester Placenta

Lymphocytic choriomeningitis virus (LCMV) is a rodent disease that can be transmitted to humans. A majority of persons infected with LCMV have only minor symptoms; however, it can cross the placental barrier during pregnancy and cause congenital defects in the fetus. Some viral infections early in gestation are hypothesized to lead to worse outcomes compared to those acquired during late gestation; however, LCMV has not been studied in this context. In the present study, differences in immunomodulation between the first- and third-trimester placental explants infected with LCMV were measured. LCMV replication was observed in the first-trimester chorionic villi, but not in term. The term placenta exhibited a robust innate immune response to infection by LCMV, marked by induction of ifn-α, il-6, and tnf-α gene expression which was not seen in the first-trimester explants. Cytokine secretion was also only seen in term explants. The results indicate that the first-trimester and term placentas differ in their permissiveness for LCMV infection, inversely correlating with the innate antiviral responses. This has implications for developing effective mechanisms that protect the fetus from infection based on stage of development.