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

被引：150

作者：

Figueiredo, Claudia P. ^{[1
]}

Barros-Aragao, Fernanda G. Q. ^{[1
,2
]}

Neris, Romulo L. S. ^{[3
]}

Frost, Paula S. ^{[1
,2
]}

Soares, Carolina ^{[1
,2
]}

Souza, Isis N. O. ^{[1
]}

Zeidler, Julianna D. ^{[4
]}

Zamberlan, Daniele C. ^{[1
]}

de Sousa, Virginia L. ^{[1
]}

Souza, Amanda S. ^{[5
]}

Guimaraes, Andre Luis A. ^{[1
]}

Bellio, Maria ^{[3
]}

de Souza, Jorge Marcondes ^{[6
,7
]}

Alves-Leon, Soniza V. ^{[6
,7
,8
]}

Neves, Gilda A. ^{[2
]}

Paula-Neto, Heitor A. ^{[1
]}

Castro, Newton G. ^{[2
]}

De Felice, Fernanda G. ^{[4
,9
,10
]}

Assuncao-Miranda, Iranaia ^{[3
]}

Clarke, Julia R. ^{[1
]}

Da Poian, Andrea T. ^{[4
]}

Ferreira, Sergio T. ^{[4
,5
]}

机构：

[1] Univ Fed Rio de Janeiro, Sch Pharm, BR-21944590 Rio De Janeiro, RJ, Brazil

[2] Univ Fed Rio de Janeiro, Inst Biomed Sci, BR-21944590 Rio De Janeiro, RJ, Brazil

[3] Univ Fed Rio de Janeiro, Inst Microbiol Paulo de Goes, BR-21944590 Rio De Janeiro, RJ, Brazil

[4] Univ Fed Rio de Janeiro, Inst Med Biochem Leopoldo de Meis, BR-21944590 Rio De Janeiro, RJ, Brazil

[5] Univ Fed Rio de Janeiro, Inst Biophys Carlos Chagas Filho, BR-21944590 Rio De Janeiro, RJ, Brazil

[6] Univ Fed Rio de Janeiro, Clementino Fraga Filho Univ Hosp, Div Neurosurg, BR-21944590 Rio De Janeiro, RJ, Brazil

[7] Univ Fed Rio de Janeiro, Clementino Fraga Filho Univ Hosp, Epilepsy Program, Div Neurol, BR-21944590 Rio De Janeiro, RJ, Brazil

[8] Queens Univ, Fed Univ Rio de Janeiro State, Grad Program Neurol, Kingston, ON, Canada

[9] Queens Univ, Ctr Neurosci Studies, Kingston, ON, Canada

[10] Queens Univ, Dept Psychiat, Kingston, ON, Canada

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷

关键词：

CENTRAL-NERVOUS-SYSTEM; A-BETA OLIGOMERS; ACTIVATION; INFECTION; COMPLICATIONS; MICROGLIA; EPIDEMIC; DISEASE; IMPACT;

D O I：

10.1038/s41467-019-11866-7

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-alpha 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-alpha 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-alpha, 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.

引用

页数：16

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