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

Frontiers in Microbiology

Paula Pezzuto¹  Renato S. de Aguiar¹  Paola P. Silveira¹  Amilcar Tanuri¹  Carolina G. de Oliveira Lucas²  Marcelo T. Bozza²  Sharton V. A. Coelho³  Lana M. Meuren³  Michelle P. Papa³  Flavio Lemos Matassoli³  Yasmin M. Mustafá³  Luciana B. de Arruda³  Pedro M. Pimentel-Coelho⁴  Loraine Campanati⁵  Heitor A. Paula Neto⁶  Mauricio L. Nogueira⁷  Milene R. Ribeiro⁷  Paula S. Frost⁸  Claudia P. Figueiredo⁸ 

[1] Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;Departamento de Virologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;Laboratório de Alvos Moleculares, Departamento de Biotecnologia Farmacêutica, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;Laboratório de Pesquisas em Virologia, Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, Brazil;Núcleo de Neurociências da Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;

关键词: Zika virus;    endothelial cells;    blood brain barrier;    transcytosis;    mouse experimental model;   

DOI  :  10.3389/fmicb.2017.02557

来源: DOAJ

【 摘 要 】

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 (ZIKVMR766 and ZIKVPE243), which induce increased production of type I and type III IFN, inflammatory cytokines and chemokines. Infection with ZIKVMR766 promoted earlier cellular death, in comparison to ZIKVPE243, 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.

【 授权许可】

Unknown