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

Lark L. Coffey, Rebekah I. Keesler, Patricia A. Pesavento, Kevin Woolard, Anil Singapuri, Jennifer Watanabe, Christina Cruzen, Kari L. Christe, Jodie Usachenko, Joann Yee, Victoria A. Heng, Eliza Bliss-Moreau, J. Rachel Reader, Wilhelm Von Morgenland, Anne M. Gibbons, Kenneth Jackson, Amir Ardeshir, Holly Heimsath, Sallie Permar, Paranthaman SenthamaraikannanPietro Presicce, Suhas G. Kallapur, Jeffrey M. Linnen, Kui Gao, Robert Orr, Tracy MacGill, Michelle McClure, Richard McFarland, John H. Morrison, Koen K.A. Van Rompay

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number2414
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Coffey, L. L., Keesler, R. I., Pesavento, P. A., Woolard, K., Singapuri, A., Watanabe, J., Cruzen, C., Christe, K. L., Usachenko, J., Yee, J., Heng, V. A., Bliss-Moreau, E., Reader, J. R., Von Morgenland, W., Gibbons, A. M., Jackson, K., Ardeshir, A., Heimsath, H., Permar, S., ... Van Rompay, K. K. A. (2018). Intraamniotic Zika virus inoculation of pregnant rhesus macaques produces fetal neurologic disease. Nature Communications, 9(1), [2414]. https://doi.org/10.1038/s41467-018-04777-6