PMID- 28362944 OWN - NLM STAT- MEDLINE DCOM- 20171222 LR - 20220316 IS - 1537-6591 (Electronic) IS - 1058-4838 (Linking) VI - 64 IP - 7 DP - 2017 Apr 1 TI - Zika Virus Infects Human Fetal Brain Microglia and Induces Inflammation. PG - 914-920 LID - 10.1093/cid/ciw878 [doi] AB - 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-alpha), interleukin 1beta (IL-1beta), and monocyte chemotactic protein 1 (MCP-1). CONCLUSIONS: Our results highlight an important role for microglia and neuroinflammation during congenital ZIKV pathogenesis. CI - (c) The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. FAU - Lum, Fok-Moon AU - Lum FM AD - Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR). FAU - Low, Donovan K S AU - Low DK AD - Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR). FAU - Fan, Yiping AU - Fan Y AD - Department of Reproductive Medicine and. FAU - Tan, Jeslin J L AU - Tan JJ AD - Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR). FAU - Lee, Bernett AU - Lee B AD - Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR). FAU - Chan, Jerry K Y AU - Chan JK AD - Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR). AD - Department of Reproductive Medicine and. AD - KK Research Centre, KK Women's and Children's Hospital, and. AD - Cancer and Stem Cell Program, Duke-NUS Medical School, Singapore; and. FAU - Renia, Laurent AU - Renia L AD - Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR). FAU - Ginhoux, Florent AU - Ginhoux F AD - Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR). FAU - Ng, Lisa F P AU - Ng LF AD - Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR). AD - Institute of Infection and Global Health, University of Liverpool, United Kingdom. LA - eng PT - Journal Article PL - United States TA - Clin Infect Dis JT - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America JID - 9203213 RN - 0 (Cytokines) SB - IM MH - Animals MH - Brain/pathology/virology MH - Cell Line MH - Cells, Cultured MH - Chlorocebus aethiops MH - Cytokines/metabolism MH - Encephalitis, Viral/immunology/metabolism/pathology/virology MH - Fetus MH - Humans MH - Macrophages/immunology/metabolism/virology MH - Microcephaly/etiology MH - Microglia/metabolism/*virology MH - Monocytes/immunology/metabolism/virology MH - Vero Cells MH - Viral Load MH - *Zika Virus MH - Zika Virus Infection/immunology/metabolism/pathology/*virology OTO - NOTNLM OT - Zika virus OT - inflammation OT - microglia. EDAT- 2017/04/01 06:00 MHDA- 2017/12/23 06:00 CRDT- 2017/04/01 06:00 PHST- 2016/10/12 00:00 [received] PHST- 2017/01/04 00:00 [accepted] PHST- 2017/04/01 06:00 [entrez] PHST- 2017/04/01 06:00 [pubmed] PHST- 2017/12/23 06:00 [medline] AID - 3041121 [pii] AID - 10.1093/cid/ciw878 [doi] PST - ppublish SO - Clin Infect Dis. 2017 Apr 1;64(7):914-920. doi: 10.1093/cid/ciw878.