Author:
Souza Isis N. O.,Frost Paula S.,França Julia V.,Nascimento-Viana Jéssica,Neris Rômulo L. S.,Freitas Leandro,Pinheiro Daniel J. L. L.,Neves Gilda,Chimelli Leila,De Felice Fernanda G.,Cavalheiro Ésper A.,Ferreira Sergio T.,Da Poian Andrea T.,Assunção-Miranda Iranaia,Figueiredo Claudia P.,Clarke Julia R.
Abstract
AbstractA causal relationship between congenital Zika virus (ZIKV) exposure and microcephaly and other neurological disorders have been established, but long-term consequences of infection are still unknown. We evaluated acute and late neuropathological and behavioral consequences of ZIKV infection in a neonatal immunocompetent mouse model. ZIKV showed brain tropism, causing post-natal microcephaly and several behavioral dysfunctions. During the acute phase of infection, mice developed very frequent epileptic seizures, which are consistently reduced by TNF-α neutralization. Although adult animals recover from seizures, they become more susceptible to chemically-induced crises. Intriguingly, the virus remained actively replicating in adult animals, which show persistent necrosis and calcifications in the mice brain. Altogether the results reveal late consequences of neonatal ZIKV exposure and suggest the early inhibition of neuroinflammation as a potential treatment.
Publisher
Cold Spring Harbor Laboratory