title: Zika virus infection induces mitosis abnormalities and apoptotic cell death of human neural progenitor cells.
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.
authors.affiliation: Gonçalo Moniz Institute, FIOCRUZ, Salvador, Bahia, 40296-710, Brazil.|Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Bahia, 41253-190, Brazil.
authors.forename: Bruno S F
authors.initials: BS
authors.lastname: Souza
authors.affiliation: Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Bahia, 41253-190, Brazil.
authors.forename: Gabriela L A
authors.initials: GL
authors.lastname: Sampaio
authors.affiliation: Gonçalo Moniz Institute, FIOCRUZ, Salvador, Bahia, 40296-710, Brazil.
authors.forename: Ciro S
authors.initials: CS
authors.lastname: Pereira
authors.affiliation: Laboratory of Virology, Federal University of Bahia, Salvador, Bahia, 40110-100, Brazil.
authors.forename: Gubio S
authors.initials: GS
authors.lastname: Campos
authors.affiliation: Laboratory of Virology, Federal University of Bahia, Salvador, Bahia, 40110-100, Brazil.
authors.forename: Silvia I
authors.initials: SI
authors.lastname: Sardi
authors.affiliation: Gonçalo Moniz Institute, FIOCRUZ, Salvador, Bahia, 40296-710, Brazil.|Department of Pathology, Federal University of Bahia Salvador, Bahia, 40110-100, Brazil.
authors.forename: Luiz A R
authors.initials: LA
authors.lastname: Freitas
authors.affiliation: Gonçalo Moniz Institute, FIOCRUZ, Salvador, Bahia, 40296-710, Brazil.
authors.forename: Claudio P
authors.initials: CP
authors.lastname: Figueira
authors.affiliation: Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Bahia, 41253-190, Brazil.
authors.forename: Bruno D
authors.initials: BD
authors.lastname: Paredes
authors.affiliation: Gonçalo Moniz Institute, FIOCRUZ, Salvador, Bahia, 40296-710, Brazil.|Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Bahia, 41253-190, Brazil.
authors.forename: Carolina K V
authors.initials: CK
authors.lastname: Nonaka
authors.affiliation: Gonçalo Moniz Institute, FIOCRUZ, Salvador, Bahia, 40296-710, Brazil.|Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Bahia, 41253-190, Brazil.
authors.forename: Carine M
authors.initials: CM
authors.lastname: Azevedo
authors.affiliation: Gonçalo Moniz Institute, FIOCRUZ, Salvador, Bahia, 40296-710, Brazil.|Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Bahia, 41253-190, Brazil.
authors.forename: Vinicius P C
authors.initials: VP
authors.lastname: Rocha
authors.affiliation: Hospital Couto Maia, Salvador, Bahia, 40425-060, Brazil.
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Bandeira
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil.
authors.forename: Rosalia
authors.initials: R
authors.lastname: Mendez-Otero
authors.affiliation: Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Bahia, 41253-190, Brazil.
authors.forename: Ricardo Ribeiro
authors.initials: RR
authors.lastname: Dos Santos
authors.affiliation: Gonçalo Moniz Institute, FIOCRUZ, Salvador, Bahia, 40296-710, Brazil.|Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Bahia, 41253-190, Brazil.
authors.forename: Milena B P
authors.initials: MB
authors.lastname: Soares
mesh_terms: D017209:Apoptosis; D002478:Cells, Cultured; D006801:Humans; D008938:Mitosis; D058953:Neural Stem Cells / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D000071244:Zika Virus / Q000378:metabolism*; D000071243:Zika Virus Infection / Q000378:metabolism* / Q000473:pathology