title: Zika Virus Infects Human Fetal Brain Microglia and Induces Inflammation.
abstract: BACKGROUND
  The unprecedented reemergence of Zika virus (ZIKV) has startled the world with reports of increased microcephaly in Brazil. ZIKV can infect human neural progenitors and impair brain growth. However, direct evidence of ZIKV infection in human fetal brain tissues remains elusive.
  
  
  METHODS
  Investigations were performed with brain cell preparations obtained from 9 donors. Virus infectivity was assessed by detection of virus antigen by flow cytometry together with various hematopoietic cell surface markers. Virus replication was determined by viral RNA quantification. Cytokine levels in supernatant obtained from virus-infected fetal brain cells were measured simultaneously in microbead-based immunoassays.
  
  
  RESULTS
  We also show that ZIKV infection was particularly evident in hematopoietic cells with microglia, the brain-resident macrophage population being one of the main targets. Infection induces high levels of proinflammatory immune mediators such as interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin 1β (IL-1β), and monocyte chemotactic protein 1 (MCP-1).
  
  
  CONCLUSIONS
  Our results highlight an important role for microglia and neuroinflammation during congenital ZIKV pathogenesis.
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR).
authors.forename: Fok-Moon
authors.initials: FM
authors.lastname: Lum
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR).
authors.forename: Donovan K S
authors.initials: DK
authors.lastname: Low
authors.affiliation: Department of Reproductive Medicine and.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR).
authors.forename: Jeslin J L
authors.initials: JJ
authors.lastname: Tan
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR).
authors.forename: Bernett
authors.initials: B
authors.lastname: Lee
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR).|Department of Reproductive Medicine and.|KK Research Centre, KK Women's and Children's Hospital, and.|Cancer and Stem Cell Program, Duke-NUS Medical School, Singapore; and.
authors.forename: Jerry K Y
authors.initials: JK
authors.lastname: Chan
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR).
authors.forename: Laurent
authors.initials: L
authors.lastname: Rénia
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR).
authors.forename: Florent
authors.initials: F
authors.lastname: Ginhoux
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR).|Institute of Infection and Global Health, University of Liverpool, United Kingdom.
authors.forename: Lisa F P
authors.initials: LF
authors.lastname: Ng
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000821:virology; D002460:Cell Line; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000378:metabolism; D018792:Encephalitis, Viral / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D005333:Fetus; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008831:Microcephaly / Q000209:etiology; D017628:Microglia / Q000378:metabolism / Q000821:virology*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D014709:Vero Cells; D019562:Viral Load; D000071244:Zika Virus; D000071243:Zika Virus Infection / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology*
chemical_list: D016207:Cytokines
keywords: Zika virus; inflammation; microglia.