Altered neurodevelopment, CSF volume, and emotional reactivity following postnatal Zika virus infection in infant macaques

Although congenital Zika virus (ZIKV) syndrome is well-characterized, the neurodevelopmental consequences of postnatal infection are understudied. We used a rhesus macaque (RM) model to investigate the consequences of postnatal ZIKV infection on brain and behavior. Male and female infant RMs infected with ZIKV at 1 month of age were compared to sex-, age-, and rearing-matched controls: uninfected and treated with Poly-IC as an innate immune control. ZIKV-infected infants showed poor state control in early infancy and increased hostility during an acute stressor. They displayed sex-specific behavioral alterations during caregiver separation though attachment bonds were preserved. MRI at 3 months revealed larger total cerebrospinal fluid (CSF) volume, reduced visual processing region volumes, and sex-specific brain structural alterations: males exhibited amygdala hypertrophy, whereas females had volumetric reductions in temporal-limbic and temporal-auditory cortices. These findings indicate that postnatal ZIKV infection is associated with alterations in sensory, social and emotion-regulatory systems and in CSF volume, that may warrant long-term monitoring of exposed children.