Intraamniotic Zika virus inoculation of pregnant rhesus macaques produces fetal neurologic disease

• Published in: Nature communications Vol. 9; no. 1; pp. 2414 - 12
• Main Authors: Coffey, Lark L., Keesler, Rebekah I., Pesavento, Patricia A., Woolard, Kevin, Singapuri, Anil, Watanabe, Jennifer, Cruzen, Christina, Christe, Kari L., Usachenko, Jodie, Yee, JoAnn, Heng, Victoria A., Bliss-Moreau, Eliza, Reader, J. Rachel, von Morgenland, Wilhelm, Gibbons, Anne M., Jackson, Kenneth, Ardeshir, Amir, Heimsath, Holly, Permar, Sallie, Senthamaraikannan, Paranthaman, Presicce, Pietro, Kallapur, Suhas G., Linnen, Jeffrey M., Gao, Kui, Orr, Robert, MacGill, Tracy, McClure, Michelle, McFarland, Richard, Morrison, John H., Van Rompay, Koen K. A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.06.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/31; 13/51; 14/32; 45/88; 631/1647/767/1424; 631/326/596/2555; 64; 692/617/375; 692/699/255/2514; 96/1; 96/106; Animals; Brain; Brain - pathology; Brain - virology; Defects; Disease Models, Animal; Female; Fetal Diseases - pathology; Fetal Diseases - virology; Fetus - pathology; Fetus - virology; Fetuses; Gestation; Humanities and Social Sciences; Humans; Infections; Inoculation; Macaca mulatta; Male; Microcephaly; Microencephaly; multidisciplinary; Nervous System Diseases - pathology; Nervous System Diseases - virology; Neuropathogenesis; Pathogenesis; Placenta; Pregnancy; Pregnancy Complications, Infectious - pathology; Pregnancy Complications, Infectious - virology; Ribonucleic acid; RNA; RNA, Viral - isolation & purification; Science; Science (multidisciplinary); Tissues; Vector-borne diseases; Viruses; Zika virus; Zika Virus - genetics; Zika Virus - isolation & purification; Zika Virus - pathogenicity; Zika Virus Infection - pathology; Zika Virus Infection - virology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-04777-6

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. Zika virus infection of pregnant women can cause congenital brain defects. Here, Coffey et al. establish a pregnant rhesus macaque model, using intravenous and intraamniotic route of infection, that reliably reproduces fetal neurologic defects of congenital Zika syndrome in humans.