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

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 replica...

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Published in:	Frontiers in microbiology Vol. 8; p. 2557
Main Authors:	Papa, Michelle P, Meuren, Lana M, Coelho, Sharton V A, Lucas, Carolina G de Oliveira, Mustafá, Yasmin M, Lemos Matassoli, Flavio, Silveira, Paola P, Frost, Paula S, Pezzuto, Paula, Ribeiro, Milene R, Tanuri, Amilcar, Nogueira, Mauricio L, Campanati, Loraine, Bozza, Marcelo T, Paula Neto, Heitor A, Pimentel-Coelho, Pedro M, Figueiredo, Claudia P, de Aguiar, Renato S, de Arruda, Luciana B
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers Media S.A 22-12-2017
Subjects:	blood brain barrier endothelial cells Microbiology mouse experimental model transcytosis Zika virus blood brain barrier endothelial cells Zika virus mouse experimental model transcytosis
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Summary:	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 model of blood brain barrier (BBB), and evaluated virus extravasation and BBB integrity in an mouse experimental model. HBMECs were productively infected by African and Brazilian ZIKV strains (ZIKV and ZIKV ), which induce increased production of type I and type III IFN, inflammatory cytokines and chemokines. Infection with ZIKV promoted earlier cellular death, in comparison to ZIKV , 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Eduardo L. V. Silveira, University of São Paulo, Brazil; Karen M. Smith, University of Louisiana at Lafayette, United States Edited by: Francois Villinger, University of Louisiana at Lafayette, United States This article was submitted to Virology, a section of the journal Frontiers in Microbiology These authors have contributed equally to this work.
ISSN:	1664-302X 1664-302X
DOI:	10.3389/fmicb.2017.02557