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

作者：de Oliveira Souza Isis Nem; Frost Paula S; Franca Julia V; Nascimento Viana Jessica B; Neris Romulo L S; Freitas Leandro; Pinheiro Daniel J L L; Nogueira Clara O; Neves Gilda; Chimelli Leila; De Felice Fernanda G; Cavalheiro Esper A; Ferreira Sergio T; Assuncao Miranda Iranaia^*; Figueiredo Claudia P^*; Da Poian Andrea T^*; Clarke Julia R^*

来源：Science Translational Medicine, 2018, 10(444): eaar2749.

DOI：10.1126/scitranslmed.aar2749

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-alpha (TNF-alpha) 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-alpha-mediated neuroinflammation might be an effective therapeutic strategy to prevent the development of chronic neurological abnormalities.

• 出版日期2018-6-6