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Sci Transl Med. 2018 Jun 6;10(444). pii: eaar2749. doi: 10.1126/scitranslmed.aar2749.

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

Author information

1
School of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21944-590, Brazil.
2
Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21944-590, Brazil.
3
Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21944-590, Brazil.
4
Department of Neurology and Neurosurgery, Escola Paulista de Medicina, Federal University of São Paulo, São Paulo, SP 04023-062, Brazil.
5
Laboratory of Neuropathology, State Institute of Brain Paulo Niemeyer, Rio de Janeiro, Brazil.
6
Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21944-590, Brazil.
7
Centre for Neuroscience Studies, Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
8
Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21944-590, Brazil.
9
Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21944-590, Brazil. juliaclarke@pharma.ufrj.br iranaiamiranda@micro.ufrj.br claufig@gmail.com dapoian@bioqmed.ufrj.br.
10
School of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21944-590, Brazil. juliaclarke@pharma.ufrj.br iranaiamiranda@micro.ufrj.br claufig@gmail.com dapoian@bioqmed.ufrj.br.
11
Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21944-590, Brazil. juliaclarke@pharma.ufrj.br iranaiamiranda@micro.ufrj.br claufig@gmail.com dapoian@bioqmed.ufrj.br.

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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