Zika virus replicates in adult human brain tissue and impairs synapses and memory in mice

Claudia P. Figueiredo (), Fernanda G. Q. Barros-Aragão, Rômulo L. S. Neris, Paula S. Frost, Carolina Soares, Isis N. O. Souza, Julianna D. Zeidler, Daniele C. Zamberlan, Virginia L. Sousa, Amanda S. Souza, André Luis A. Guimarães, Maria Bellio, Jorge Marcondes de Souza, Soniza V. Alves-Leon, Gilda A. Neves, Heitor A. Paula-Neto, Newton G. Castro, Fernanda G. De Felice, Iranaia Assunção-Miranda, Julia R. Clarke, Andrea T. Da Poian () and Sergio T. Ferreira ()
Additional contact information
Claudia P. Figueiredo: Federal University of Rio de Janeiro
Fernanda G. Q. Barros-Aragão: Federal University of Rio de Janeiro
Rômulo L. S. Neris: Federal University of Rio de Janeiro
Paula S. Frost: Federal University of Rio de Janeiro
Carolina Soares: Federal University of Rio de Janeiro
Isis N. O. Souza: Federal University of Rio de Janeiro
Julianna D. Zeidler: Federal University of Rio de Janeiro
Daniele C. Zamberlan: Federal University of Rio de Janeiro
Virginia L. Sousa: Federal University of Rio de Janeiro
Amanda S. Souza: Federal University of Rio de Janeiro
André Luis A. Guimarães: Federal University of Rio de Janeiro
Maria Bellio: Federal University of Rio de Janeiro
Jorge Marcondes de Souza: Federal University of Rio de Janeiro
Soniza V. Alves-Leon: Federal University of Rio de Janeiro
Gilda A. Neves: Federal University of Rio de Janeiro
Heitor A. Paula-Neto: Federal University of Rio de Janeiro
Newton G. Castro: Federal University of Rio de Janeiro
Fernanda G. De Felice: Federal University of Rio de Janeiro
Iranaia Assunção-Miranda: Federal University of Rio de Janeiro
Julia R. Clarke: Federal University of Rio de Janeiro
Andrea T. Da Poian: Federal University of Rio de Janeiro
Sergio T. Ferreira: Federal University of Rio de Janeiro

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: Abstract Neurological complications affecting the central nervous system have been reported in adult patients infected by Zika virus (ZIKV) but the underlying mechanisms remain unknown. Here, we report that ZIKV replicates in human and mouse adult brain tissue, targeting mature neurons. ZIKV preferentially targets memory-related brain regions, inhibits hippocampal long-term potentiation and induces memory impairment in adult mice. TNF-α upregulation, microgliosis and upregulation of complement system proteins, C1q and C3, are induced by ZIKV infection. Microglia are found to engulf hippocampal presynaptic terminals during acute infection. Neutralization of TNF-α signaling, blockage of microglial activation or of C1q/C3 prevent synapse and memory impairment in ZIKV-infected mice. Results suggest that ZIKV induces synapse and memory dysfunction via aberrant activation of TNF-α, microglia and complement. Our findings establish a mechanism by which ZIKV affects the adult brain, and point to the need of evaluating cognitive deficits as a potential comorbidity in ZIKV-infected adults.

Date: 2019
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DOI: 10.1038/s41467-019-11866-7

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