Inoculation of the neonatal rat with lymphocytic choriomeningitis virus (LCMV) results in the selectiveLymphocytic choriomeningitis virus (LCMV) is a rodentborne arenavirus and a prevalent human pathogen (11,12,29). Infection of the postnatal human with LCMV typically results in only a mild febrile illness, from which the patient recovers fully. In contrast, when the infection occurs during pregnancy, the fetal brain can be severely damaged. Microencephaly, chorioretinitis, hydrocephalus, and periventricular calcifications are frequently noted features (6,18,46). These neuropathological changes lead to mental retardation, impaired coordination, spasticity, blindness, and epilepsy in children with congenital LCMV infection (5,7,46). The pathogenic mechanisms underlying LCMV-induced injury of the fetal human brain are unknown.Although the human fetal brain is vulnerable throughout gestation to the teratogenic effects of LCMV, many of the case reports of congenital LCMV infection describe infants who were infected during the third or late second trimester (21,23,42,46). This is a period of rapid brain growth, referred to as the brain growth spurt (17), and is a time when many neuroteratogens exert adverse effects (9,15). While all mammalian species have a brain growth spurt, the timing of this event, relative to birth, varies among the species. Relative to the human brain, the rat brain is immature at birth, and the brain growth spurt in the rat occurs during the first two postnatal weeks (16,17). Therefore, an accurate model of human mid-or late-gestation LCMV infection requires infection of the rat during early postnatal life.The neonatal rat inoculated with LCMV serves as an excellent model system for human congenital LCMV infection. LCMV infection in suckling rats induces microencephaly, retinitis, and the selective destruction of several brain regions (32,34,38). These neuropathologic changes manifest as permanent abnormalities of movement, coordination, vision, and behavior, reminiscent of human congenital LCMV infection (14,30,31).In the neonatal rat brain, inoculation of LCMV induces a distinct pattern of infection in which specific neuronal populations are consistently infected, while others are spared (13,34). This selectivity of infection likely underlies the focal pathological changes which follow. However, the susceptible neuronal populations are widely separated, and the pathway by which LCMV reaches these neurons has not been identified. Elucidation of this pathway is of substantial importance, not only for a better understanding of LCMV biology and teratogenesis, but because the cells utilized by LCMV in its sequential spread are sites to which therapeutic agents could be targeted to block the infection.One goal of this study was to examine the sequential migration of LCMV in the developing brain to identify the pathway by which LCMV reaches susceptible neurons. The results demonstrate that glial cells are the initial target cells of LCMV within the brain parenchyma and that LCMV spreads across the ...
