PMID- 29925843 OWN - NLM STAT- MEDLINE DCOM- 20190116 LR - 20190620 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 9 IP - 1 DP - 2018 Jun 20 TI - Intraamniotic Zika virus inoculation of pregnant rhesus macaques produces fetal neurologic disease. PG - 2414 LID - 10.1038/s41467-018-04777-6 [doi] LID - 2414 AB - Zika virus (ZIKV) infection of pregnant women can cause fetal microcephaly and other neurologic defects. We describe the development of a non-human primate model to better understand fetal pathogenesis. To reliably induce fetal infection at defined times, four pregnant rhesus macaques are inoculated intravenously and intraamniotically with ZIKV at gestational day (GD) 41, 50, 64, or 90, corresponding to first and second trimester of gestation. The GD41-inoculated animal, experiencing fetal death 7 days later, has high virus levels in fetal and placental tissues, implicating ZIKV as cause of death. The other three fetuses are carried to near term and euthanized; while none display gross microcephaly, all show ZIKV RNA in many tissues, especially in the brain, which exhibits calcifications and reduced neural precursor cells. Given that this model consistently recapitulates neurologic defects of human congenital Zika syndrome, it is highly relevant to unravel determinants of fetal neuropathogenesis and to explore interventions. FAU - Coffey, Lark L AU - Coffey LL AUID- ORCID: 0000-0002-0718-5146 AD - Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, 1 Shields Avenue, Davis, CA, 95616, USA. lcoffey@ucdavis.edu. FAU - Keesler, Rebekah I AU - Keesler RI AD - California National Primate Research Center, University of California, 1 Shields Avenue, Davis, CA, 95616, USA. FAU - Pesavento, Patricia A AU - Pesavento PA AD - Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, 1 Shields Avenue, Davis, CA, 95616, USA. FAU - Woolard, Kevin AU - Woolard K AD - Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, 1 Shields Avenue, Davis, CA, 95616, USA. FAU - Singapuri, Anil AU - Singapuri A AD - Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, 1 Shields Avenue, Davis, CA, 95616, USA. FAU - Watanabe, Jennifer AU - Watanabe J AD - California National Primate Research Center, University of California, 1 Shields Avenue, Davis, CA, 95616, USA. FAU - Cruzen, Christina AU - Cruzen C AD - California National Primate Research Center, University of California, 1 Shields Avenue, Davis, CA, 95616, USA. FAU - Christe, Kari L AU - Christe KL AD - California National Primate Research Center, University of California, 1 Shields Avenue, Davis, CA, 95616, USA. FAU - Usachenko, Jodie AU - Usachenko J AD - California National Primate Research Center, University of California, 1 Shields Avenue, Davis, CA, 95616, USA. FAU - Yee, JoAnn AU - Yee J AD - California National Primate Research Center, University of California, 1 Shields Avenue, Davis, CA, 95616, USA. FAU - Heng, Victoria A AU - Heng VA AD - California National Primate Research Center, University of California, 1 Shields Avenue, Davis, CA, 95616, USA. AD - Donders Institute, Radboud University, Montessorilaan 3, 6525 HR, Nijmegen, The Netherlands. FAU - Bliss-Moreau, Eliza AU - Bliss-Moreau E AD - California National Primate Research Center, University of California, 1 Shields Avenue, Davis, CA, 95616, USA. AD - Department of Psychology, University of California, 1 Shields Avenue, Davis, CA, 95616, USA. FAU - Reader, J Rachel AU - Reader JR AUID- ORCID: 0000-0003-3864-6731 AD - California National Primate Research Center, University of California, 1 Shields Avenue, Davis, CA, 95616, USA. FAU - von Morgenland, Wilhelm AU - von Morgenland W AD - California National Primate Research Center, University of California, 1 Shields Avenue, Davis, CA, 95616, USA. FAU - Gibbons, Anne M AU - Gibbons AM AD - California National Primate Research Center, University of California, 1 Shields Avenue, Davis, CA, 95616, USA. FAU - Jackson, Kenneth AU - Jackson K AD - Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, 1 Shields Avenue, Davis, CA, 95616, USA. FAU - Ardeshir, Amir AU - Ardeshir A AUID- ORCID: 0000-0002-4330-4659 AD - California National Primate Research Center, University of California, 1 Shields Avenue, Davis, CA, 95616, USA. FAU - Heimsath, Holly AU - Heimsath H AD - Duke Human Vaccine Institute, Duke University Medical Center, 103020, 2 Genome Court MSRBII, Durham, NC, 27710, USA. FAU - Permar, Sallie AU - Permar S AD - Duke Human Vaccine Institute, Duke University Medical Center, 103020, 2 Genome Court MSRBII, Durham, NC, 27710, USA. FAU - Senthamaraikannan, Paranthaman AU - Senthamaraikannan P AUID- ORCID: 0000-0002-3333-3720 AD - Division of Neonatology and Pulmonary Biology, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA. FAU - Presicce, Pietro AU - Presicce P AD - Divisions of Neonatology and Developmental Biology, David Geffen School of Medicine at the University of California, 10833 Le Conte Avenue, Los Angeles, CA, 90095, USA. FAU - Kallapur, Suhas G AU - Kallapur SG AD - Divisions of Neonatology and Developmental Biology, David Geffen School of Medicine at the University of California, 10833 Le Conte Avenue, Los Angeles, CA, 90095, USA. FAU - Linnen, Jeffrey M AU - Linnen JM AD - Grifols Diagnostic Solutions, Inc., 10808 Willow Court, San Diego, CA, 92127, USA. FAU - Gao, Kui AU - Gao K AD - Grifols Diagnostic Solutions, Inc., 10808 Willow Court, San Diego, CA, 92127, USA. FAU - Orr, Robert AU - Orr R AD - Office of Counterterrorism and Emerging Threats, Office of the Chief Scientist, Food and Drug Administration, 25 New Hampshire Avenue, Silver Spring, MD, 20903, USA. FAU - MacGill, Tracy AU - MacGill T AD - Office of Counterterrorism and Emerging Threats, Office of the Chief Scientist, Food and Drug Administration, 25 New Hampshire Avenue, Silver Spring, MD, 20903, USA. FAU - McClure, Michelle AU - McClure M AD - Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD, 20903, USA. FAU - McFarland, Richard AU - McFarland R AD - The Advanced Regenerative Manufacturing Institute, 400 Commercial Street, Manchester, NH, 03101, USA. FAU - Morrison, John H AU - Morrison JH AD - California National Primate Research Center, University of California, 1 Shields Avenue, Davis, CA, 95616, USA. FAU - Van Rompay, Koen K A AU - Van Rompay KKA AUID- ORCID: 0000-0002-7375-1337 AD - California National Primate Research Center, University of California, 1 Shields Avenue, Davis, CA, 95616, USA. kkvanrompay@ucdavis.edu. LA - eng GR - P51 OD011107/OD/NIH HHS/United States GR - R21 AI129479/AI/NIAID NIH HHS/United States GR - P51OD011107/UC | UC Davis | California National Primate Research Center (CNPRC)/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180620 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (RNA, Viral) SB - IM MH - Animals MH - Brain/pathology/virology MH - *Disease Models, Animal MH - Female MH - Fetal Diseases/*pathology/virology MH - Fetus/pathology/virology MH - Humans MH - *Macaca mulatta MH - Male MH - Nervous System Diseases/*pathology/virology MH - Pregnancy MH - Pregnancy Complications, Infectious/*pathology/virology MH - RNA, Viral/isolation & purification MH - Zika Virus/genetics/isolation & purification/*pathogenicity MH - Zika Virus Infection/*pathology/virology PMC - PMC6010452 COIS- J.M.L. and K.G. are employees of Grifols Diagnostics Solutions, Inc. They tested selected maternal tissues for ZIKV RNA. They did not influence the interpretations in the manuscript. The remaining authors declare no competing interests. EDAT- 2018/06/22 06:00 MHDA- 2019/01/17 06:00 PMCR- 2018/06/20 CRDT- 2018/06/22 06:00 PHST- 2017/11/27 00:00 [received] PHST- 2018/04/10 00:00 [accepted] PHST- 2018/06/22 06:00 [entrez] PHST- 2018/06/22 06:00 [pubmed] PHST- 2019/01/17 06:00 [medline] PHST- 2018/06/20 00:00 [pmc-release] AID - 10.1038/s41467-018-04777-6 [pii] AID - 4777 [pii] AID - 10.1038/s41467-018-04777-6 [doi] PST - epublish SO - Nat Commun. 2018 Jun 20;9(1):2414. doi: 10.1038/s41467-018-04777-6.