Research ArticleEMERGING INFECTIONS

Postnatal Zika virus infection is associated with persistent abnormalities in brain structure, function, and behavior in infant macaques

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Science Translational Medicine  04 Apr 2018:
Vol. 10, Issue 435, eaao6975
DOI: 10.1126/scitranslmed.aao6975

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Postnatal perturbation by Zika virus

Much of the concern surrounding Zika virus infections focuses on fetuses infected in utero. Mavigner et al. reasoned that this neurotropic virus may have deleterious effects even after birth, so they set up a postnatal infection model to investigate. They found that infant rhesus macaques infected with Zika virus also had peripheral and central nervous system pathology. Longitudinal magnetic resonance imaging studies revealed that macaques that had been infected with Zika virus had structural and functional abnormalities and also altered emotional responses. These differences persisted months after the virus had been cleared. Although the work involved a small number of animals, their results suggest that infants and young children exposed to Zika virus should undergo more than just routine monitoring.

Abstract

The Zika virus (ZIKV) epidemic is associated with fetal brain lesions and other serious birth defects classified as congenital ZIKV syndrome. Postnatal ZIKV infection in infants and children has been reported; however, data on brain anatomy, function, and behavioral outcomes following infection are absent. We show that postnatal ZIKV infection of infant rhesus macaques (RMs) results in persistent structural and functional alterations of the central nervous system compared to age-matched controls. We demonstrate ZIKV lymphoid tropism and neurotropism in infant RMs and histopathologic abnormalities in the peripheral and central nervous systems including inflammatory infiltrates, astrogliosis, and Wallerian degeneration. Structural and resting-state functional magnetic resonance imaging (MRI/rs-fMRI) show persistent enlargement of lateral ventricles, maturational changes in specific brain regions, and altered functional connectivity (FC) between brain areas involved in emotional behavior and arousal functions, including weakened amygdala-hippocampal connectivity in two of two ZIKV-infected infant RMs several months after clearance of ZIKV RNA from peripheral blood. ZIKV infection also results in distinct alterations in the species-typical emotional reactivity to acute stress, which were predicted by the weak amygdala-hippocampal FC. We demonstrate that postnatal ZIKV infection of infants in this model affects neurodevelopment, suggesting that long-term clinical monitoring of pediatric cases is warranted.

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