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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Zika Virus Infects, Activates, and Crosses Brain Microvascular Endothelial Cells, without Barrier Disruption

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Author(s):
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Papa, Michelle P. [1] ; Meuren, Lana M. [1] ; Coelho, Sharton V. A. [1] ; de Oliveira Lucas, Carolina G. [2, 1] ; Mustafa, Yasmin M. [1] ; Matassoli, Flavio Lemos [1] ; Silveira, Paola P. [3] ; Frost, Paula S. [4] ; Pezzuto, Paula [3] ; Ribeiro, Milene R. [5] ; Tanuri, Amilcar [3] ; Nogueira, Mauricio L. [5] ; Campanati, Loraine [6] ; Bozza, Marcelo T. [2] ; Paula Neto, Heitor A. [7] ; Pimentel-Coelho, Pedro M. [8] ; Figueiredo, Claudia P. [4] ; de Aguiar, Renato S. [3] ; de Arruda, Luciana B. [1]
Total Authors: 19
Affiliation:
[1] Univ Fed Rio de Janeiro, Inst Microbiol Paulo Goes, Dept Virol, Rio De Janeiro - Brazil
[2] Univ Fed Rio de Janeiro, Inst Microbiol Paulo Goes, Dept Imunol, Rio De Janeiro - Brazil
[3] Univ Fed Rio de Janeiro, Inst Biol, Dept Genet, Rio De Janeiro - Brazil
[4] Univ Fed Rio de Janeiro, Fac Farm, Nucleo Neurociencias, Rio De Janeiro - Brazil
[5] Fac Med Sao Jose Do Rio Preto, Lab Pesquisas Virol, Sao Jose Do Rio Preto - Brazil
[6] Univ Fed Rio de Janeiro, Inst Ciencias Biomed, Rio De Janeiro - Brazil
[7] Univ Fed Rio de Janeiro, Fac Farm, Dept Biotecnol Farmaceut, Lab Alvos Mol, Rio De Janeiro - Brazil
[8] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Rio de Janeiro - Brazil
Total Affiliations: 8
Document type: Journal article
Source: FRONTIERS IN MICROBIOLOGY; v. 8, DEC 22 2017.
Web of Science Citations: 23
Abstract

Zika virus (ZIKV) has been associated to central nervous system (CNS) harm, and virus was detected in the brain and cerebrospinal fluids of microcephaly and meningoencephalitis cases. However, the mechanism by which the virus reaches the CNS is unclear. Here, we addressed the effects of ZIKV replication in human brain microvascular endothelial cells (HBMECs), as an in vitro model of blood brain barrier (BBB), and evaluated virus extravasation and BBB integrity in an in vivo mouse experimental model. HBMECs were productively infected by African and Brazilian ZIKV strains (ZIKV(MR766) and ZIKV(PE243)), which induce increased production of type I and type III IFN, inflammatory cytokines and chemokines. Infection with ZIKV(MR766) promoted earlier cellular death, in comparison to ZIKV(PE243), but infection with either strain did not result in enhanced endothelial permeability. Despite the maintenance of endothelial integrity, infectious virus particles crossed the monolayer by endocytosis/exocytosis-dependent replication pathway or by transcytosis. Remarkably, both viruses' strains infected IFNAR deficient mice, with high viral load being detected in the brains, without BBB disruption, which was only detected at later time points after infection. These data suggest that ZIKV infects and activates endothelial cells, and might reach the CNS through basolateral release, transcytosis or transinfection processes. These findings further improve the current knowledge regarding ZIKV dissemination pathways. (AU)

FAPESP's process: 13/21719-3 - Epidemiological study of dengue (serotypes1-4) in a cohort of São José do Rio Preto, São Paulo, Brazil, during 2014-2018
Grantee:Maurício Lacerda Nogueira
Support Opportunities: Research Projects - Thematic Grants