Impairment in neurocognitive function following experimental neonatal guinea pig cytomegalovirus infection.

Abstract

BACKGROUND:Cytomegalovirus (CMV) is a leading infectious cause of neurologic deficits, both in the settings of congenital and perinatal infection, but few animal models exist to study neurodevelopmental outcomes. This study examined the impact of neonatal guinea pig CMV (GPCMV) infection on spatial learning and memory in a Morris water maze (MWM) model.METHODS:Newborn pups were challenged intraperitoneally (ip) with a pathogenic red fluorescent protein (RFP)-tagged GPCMV, or sham-inoculated. On days 15–19 post-infection (pi), pups were tested in the MWM. Viral loads were measured in blood and tissue by quantitative PCR (qPCR), and brain samples collected at necropsy were examined by histology and immunohistochemistry.RESULTS:Viremia (DNAemia) was detected at day 3 pi in 7/8 challenged animals. End-organ dissemination was observed, by qPCR, in lung, liver, and spleen. CD4+ and CD8+ T-cell infiltrates were present in brains of challenged animals, particularly in periventricular and hippocampal regions. Reactive gliosis and microglial nodules were observed. Statistically significant spatial learning and memory deficits were observed by MWM, particularly for total maze distance travelled (p<0.0001).CONCLUSION:Neonatal GPCMV infection in guinea pigs results in cognitive defects demonstrable by the MWM. This neonatal guinea pig challenge model can be exploited for studying antiviral interventions.