Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/17924
Title: Zika virus infection induces mitosis abnormalities and apoptotic cell death of human neural progenitor cells
Authors: Souza, Bruno Solano de Freitas
Sampaio, Gabriela Louise de Almeida
Pereira, Ciro Silveira e
Campos, Gubio Soares
Sardi, Silvia I
Freitas, Luiz Antonio Rodrigues de
Figueira, Claudio Pereira
Paredes, Bruno D
Nonaka, Carolina K V
Azevedo, Carine Machado
Rocha, Vinicius Pinto Costa
Bandeira, Antonio Carlos de Albuquerque
Otero, Rosalia Mendez
Santos, Ricardo Ribeiro dos
Soares, Milena Botelho Pereira
Affilliation: Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / São Rafael Hospital. Center for Biotechnology and Cell Therapy. Salvador, BA, Brasil
São Rafael Hospital. Center for Biotechnology and Cell Therapy. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil
Federal University of Bahia. Laboratory of Virology, Salvador, BA, Brasil
Federal University of Bahia. Laboratory of Virology, Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Department of Pathology. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil
São Rafael Hospital. Center for Biotechnology and Cell Therapy. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / São Rafael Hospital. Center for Biotechnology and Cell Therapy. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / São Rafael Hospital. Center for Biotechnology and Cell Therapy. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / São Rafael Hospital. Center for Biotechnology and Cell Therapy. Salvador, BA, Brasil
Hospital Couto Maia. Salvador, BA, Brasil
Federal University of Rio de Janeiro. Institute of Biophysics Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil
São Rafael Hospital. Center for Biotechnology and Cell Therapy. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / São Rafael Hospital. Center for Biotechnology and Cell Therapy. Salvador, BA, Brasil
Abstract: Zika virus (ZIKV) infection has been associated with severe complications both in the developing and adult nervous system. To investigate the deleterious effects of ZIKV infection, we used human neural progenitor cells (NPC), derived from induced pluripotent stem cells (iPSC). We found that NPC are highly susceptible to ZIKV and the infection results in cell death. ZIKV infection led to a marked reduction in cell proliferation, ultrastructural alterations and induction of autophagy. Induction of apoptosis of Sox2(+) cells was demonstrated by activation of caspases 3/7, 8 and 9, and by ultrastructural and flow cytometry analyses. ZIKV-induced death of Sox2(+) cells was prevented by incubation with the pan-caspase inhibitor, Z-VAD-FMK. By confocal microscopy analysis we found an increased number of cells with supernumerary centrosomes. Live imaging showed a significant increase in mitosis abnormalities, including multipolar spindle, chromosome laggards, micronuclei and death of progeny after cell division. FISH analysis for chromosomes 12 and 17 showed increased frequency of aneuploidy, such as monosomy, trisomy and polyploidy. Our study reinforces the link between ZIKV and abnormalities in the developing human brain, including microcephaly.
Keywords: Zika Virus
Infection
Brain
Abnormalities nervous system
Humans
Microcephaly
keywords: Zika virus
Infecção
Cérebro
Anormalidades do Sistema Nervoso
Humanos
Microcefalia
Issue Date: 2016
Publisher: Nature Publishing Group
Citation: SOUZA, B. S. F. et al. Zika virus infection induces mitosis abnormalities and apoptotic cell death of human neural progenitor cells. Scientific Reports, v. 6, p. 39775, 2016.
DOI: 10.1038/srep39775
ISSN: 2045-2322
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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