title: Zika virus disrupts molecular fingerprinting of human neurospheres.
abstract: Zika virus (ZIKV) has been associated with microcephaly and other brain abnormalities; however, the molecular consequences of ZIKV to human brain development are still not fully understood. Here we describe alterations in human neurospheres derived from induced pluripotent stem (iPS) cells infected with the strain of Zika virus that is circulating in Brazil. Combining proteomics and mRNA transcriptional profiling, over 500 proteins and genes associated with the Brazilian ZIKV infection were found to be differentially expressed. These genes and proteins provide an interactome map, which indicates that ZIKV controls the expression of RNA processing bodies, miRNA biogenesis and splicing factors required for self-replication. It also suggests that impairments in the molecular pathways underpinning cell cycle and neuronal differentiation are caused by ZIKV. These results point to biological mechanisms implicated in brain malformations, which are important to further the understanding of ZIKV infection and can be exploited as therapeutic potential targets to mitigate it.
authors.affiliation: D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.|Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Patricia P
authors.initials: PP
authors.lastname: Garcez
authors.affiliation: D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.|Institute of Biology, Department of Biochemistry and Tissue Biology, University of Campinas (UNICAMP), Campinas, Brazil.
authors.forename: Juliana Minardi
authors.initials: JM
authors.lastname: Nascimento
authors.affiliation: Center for Technological Innovation, Evandro Chagas Institute, Belém, Brazil.
authors.forename: Janaina Mota
authors.initials: JM
authors.lastname: de Vasconcelos
authors.affiliation: D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Madeiro da Costa
authors.affiliation: Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Delvecchio
authors.affiliation: D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.
authors.forename: Pablo
authors.initials: P
authors.lastname: Trindade
authors.affiliation: D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.
authors.forename: Erick Correia
authors.initials: EC
authors.lastname: Loiola
authors.affiliation: Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Luiza M
authors.initials: LM
authors.lastname: Higa
authors.affiliation: Institute of Biology, Department of Biochemistry and Tissue Biology, University of Campinas (UNICAMP), Campinas, Brazil.
authors.forename: Juliana S
authors.initials: JS
authors.lastname: Cassoli
authors.affiliation: D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Vitória
authors.affiliation: Institute Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Sequeira
authors.affiliation: D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Sochacki
authors.affiliation: Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Renato S
authors.initials: RS
authors.lastname: Aguiar
authors.affiliation: Federal University of Pará, Belém, Brazil.
authors.forename: Hellen Thais
authors.initials: HT
authors.lastname: Fuzii
authors.affiliation: Institute Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Ana M Bispo
authors.initials: AM
authors.lastname: de Filippis
authors.affiliation: Center for Technological Innovation, Evandro Chagas Institute, Belém, Brazil.
authors.forename: João Lídio
authors.initials: JL
authors.lastname: da Silva Gonçalves Vianez Júnior
authors.affiliation: Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Amilcar
authors.initials: A
authors.lastname: Tanuri
authors.affiliation: Institute of Biology, Department of Biochemistry and Tissue Biology, University of Campinas (UNICAMP), Campinas, Brazil.
authors.forename: Daniel
authors.initials: D
authors.lastname: Martins-de-Souza
authors.affiliation: D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.|Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Stevens K
authors.initials: SK
authors.lastname: Rehen
mesh_terms: D015415:Biomarkers; D002453:Cell Cycle / Q000235:genetics; D023281:Genomics / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000821:virology; D010802:Phylogeny; D020543:Proteome; D059467:Transcriptome; D000071244:Zika Virus / Q000502:physiology*; D000071243:Zika Virus Infection / Q000235:genetics* / Q000378:metabolism* / Q000821:virology
chemical_list: D015415:Biomarkers; D020543:Proteome