TY - JOUR
T1 - Intraamniotic Zika virus inoculation of pregnant rhesus macaques produces fetal neurologic disease
AU - Coffey, Lark L.
AU - Keesler, Rebekah I.
AU - Pesavento, Patricia A.
AU - Woolard, Kevin
AU - Singapuri, Anil
AU - Watanabe, Jennifer
AU - Cruzen, Christina
AU - Christe, Kari L.
AU - Usachenko, Jodie
AU - Yee, Joann
AU - Heng, Victoria A.
AU - Bliss-Moreau, Eliza
AU - Reader, J. Rachel
AU - Von Morgenland, Wilhelm
AU - Gibbons, Anne M.
AU - Jackson, Kenneth
AU - Ardeshir, Amir
AU - Heimsath, Holly
AU - Permar, Sallie
AU - Senthamaraikannan, Paranthaman
AU - Presicce, Pietro
AU - Kallapur, Suhas G.
AU - Linnen, Jeffrey M.
AU - Gao, Kui
AU - Orr, Robert
AU - MacGill, Tracy
AU - McClure, Michelle
AU - McFarland, Richard
AU - Morrison, John H.
AU - Van Rompay, Koen K.A.
N1 - Funding Information:
We acknowledge the research and support staff at CNPRC for their assistance with all aspects of the study, as well as the UC Davis IACUC and Environmental Health and Safety Offices for expedited approval for work on this project. Sarah Mills, Abigail Spinner, and the staff of the Pathogen Detection Laboratory, Clinical Laboratories and Colony Research Services at CNPRC helped with procedures, necropsies and biospeci-men processing, and analysis. Kathy West provided illustrations. The Zika research team at the Wisconsin National Primate Research Center provided ongoing advice and data sharing. This study was supported by a CNPRC pilot research grant to L.L.C. and K.K.A. v.R., the Office of Research Infrastructure Programs/OD (P51OD011107), start up funds from the Pathology, Microbiology and Immunology Department, and 1R21AI129479-01 to K.K.A.v.R. This effort was partially funded by the United States Food and Drug Administration (FDA), via contract #HHSF223201610542P “Companion Studies to Define the Distribution and Duration of Zika virus Infection in Non-Human Primates”. The views, opinions, and/or findings contained in this report are those of the authors and not necessarily those of the FDA.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85048857867&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-04777-6
DO - 10.1038/s41467-018-04777-6
M3 - Article
C2 - 29925843
AN - SCOPUS:85048857867
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2414
ER -