Highly efficient maternal-fetal Zika virus transmission in pregnant rhesus macaques

Sydney M. Nguyen, Kathleen M. Antony, Dawn M. Dudley, Sarah Kohn, Heather A. Simmons, Bryce Wolfe, M. Shahriar Salamat, Leandro B.C. Teixeira, Gregory J. Wiepz, Troy H. Thoong, Matthew T Aliota, Andrea M. Weiler, Gabrielle L. Barry, Kim L. Weisgrau, Logan J. Vosler, Mariel S. Mohns, Meghan E. Breitbach, Laurel M. Stewart, Mustafa N. Rasheed, Christina M. NewmanMichael E. Graham, Oliver E. Wieben, Patrick A. Turski, Kevin M. Johnson, Jennifer Post, Jennifer M. Hayes, Nancy Schultz-Darken, Michele L. Schotzko, Josh A. Eudailey, Sallie R. Permar, Eva G. Rakasz, Emma L. Mohr, Saverio Capuano, Alice F. Tarantal, Jorge E. Osorio, Shelby L. O’Connor, Thomas C. Friedrich, David H. O’Connor, Thaddeus G. Golos

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

Infection with Zika virus (ZIKV) is associated with human congenital fetal anomalies. To model fetal outcomes in nonhuman primates, we administered Asian-lineage ZIKV subcutaneously to four pregnant rhesus macaques. While non-pregnant animals in a previous study contemporary with the current report clear viremia within 10–12 days, maternal viremia was prolonged in 3 of 4 pregnancies. Fetal head growth velocity in the last month of gestation determined by ultrasound assessment of head circumference was decreased in comparison with biparietal diameter and femur length within each fetus, both within normal range. ZIKV RNA was detected in tissues from all four fetuses at term cesarean section. In all pregnancies, neutrophilic infiltration was present at the maternal-fetal interface (decidua, placenta, fetal membranes), in various fetal tissues, and in fetal retina, choroid, and optic nerve (first trimester infection only). Consistent vertical transmission in this primate model may provide a platform to assess risk factors and test therapeutic interventions for interruption of fetal infection. The results may also suggest that maternal-fetal ZIKV transmission in human pregnancy may be more frequent than currently appreciated.

Original languageEnglish (US)
Article numbere1006378
JournalPLoS pathogens
Volume13
Issue number5
DOIs
StatePublished - May 2017

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health grants R01 AI107157-01A1 to TGG, R01 AI116382-01A1S1 to DHO, DP2HD075699 to SRP and P51 OD011106 to the Wisconsin National Primate Research Center. This research was conducted in part at a facility constructed with support from Research Facilities Improvement Program grant numbers RR15459-01 and RR020141-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of Office of Research Infrastructure Program or the National Institutes of Health; https://www.nih.gov/, http://dpcpsi.nih.gov/orip/index. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank the WNPRC Veterinary, Scientific Protocol Implementation, and Pathology Services staff for assistance with animal procedures, including breeding, ultrasound monitoring, and sample collection, and Ms. Rebecca Black for editorial assistance. We thank Adam Ericsen, Jenna Kropp, and Jiro Wada for help in figure design and illustration.

Publisher Copyright:
© 2017 Nguyen et al.

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