Research ArticleZIKA

Acute and chronic neurological consequences of early-life Zika virus infection in mice

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Science Translational Medicine  06 Jun 2018:
Vol. 10, Issue 444, eaar2749
DOI: 10.1126/scitranslmed.aar2749

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Zika leaves lasting impact on brain

Perinatal Zika virus (ZIKV) infection has been associated with brain alterations in newborns. However, whether ZIKV exposure during development has long-term neurological consequences is not completely understood. Nem de Oliveira Souza et al. report that newborn mice infected with ZIKV develop acute brain abnormalities. During adulthood, perinatally infected mice showed persistent viral replication, neuropathological alterations, behavioral impairments, and altered brain excitability. Blocking tumor necrosis factor–α (TNF-α) early after infection prevented this hyperexcitability in mouse brain. The results suggest that anti-inflammatory treatments might be used to prevent the persistent increase in neuronal excitability induced by ZIKV infection in brain tissue.

Abstract

Although congenital Zika virus (ZIKV) exposure has been associated with microcephaly and other neurodevelopmental disorders, long-term consequences of perinatal infection are largely unknown. We evaluated short- and long-term neuropathological and behavioral consequences of neonatal ZIKV infection in mice. ZIKV showed brain tropism, causing postnatal-onset microcephaly and several behavioral deficits in adulthood. During the acute phase of infection, mice developed frequent seizures, which were reduced by tumor necrosis factor–α (TNF-α) inhibition. During adulthood, ZIKV replication persisted in neonatally infected mice, and the animals showed increased susceptibility to chemically induced seizures, neurodegeneration, and brain calcifications. Altogether, the results show that neonatal ZIKV infection has long-term neuropathological and behavioral complications in mice and suggest that early inhibition of TNF-α–mediated neuroinflammation might be an effective therapeutic strategy to prevent the development of chronic neurological abnormalities.

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