Early postnatal respiratory viral infection alters hippocampal neurogenesis, cell fate, and neuron morphology in the neonatal piglet

Respiratory viral infections are common during the neonatal period in humans, but little is known about how early-life infection impacts brain development. The current study used a neonatal piglet model as piglets have a gyrencephalic brain with growth and development similar to human infants. Piglets were inoculated with porcine reproductive and respiratory syndrome virus (PRRSV) to evaluate how chronic neuroinflammation affects hippocampal neurogenesis and neuron morphology. Piglets in the neurogenesis study received one bromodeoxyuridine injection on postnatal day (PD) 7 and then were inoculated with PRRSV. Piglets were sacrificed at PD 28 and the number of BrdU+ cells and cell fate were quantified in the dentate gyrus. PRRSV piglets showed a 24% reduction in the number of newly divided cells forming neurons. Approximately 15% of newly divided cells formed microglia, but this was not affected by sex or PRRSV. Additionally, there was a sexual dimorphism of new cell survival in the dentate gyrus where males had more cells than females, and PRRSV infection caused a decreased survival in males only. Golgi impregnation was used to characterize dentate granule cell morphology. Sholl analysis revealed that PRRSV caused a change in inner granule cell morphology where the first branch point was extended further from the cell body. Males had more complex dendritic arbors than females in the outer granule cell layer, but this was not affected by PRRSV. There were no changes to dendritic spine density or morphology distribution. These findings suggest that early-life viral infection can impact brain development.