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Highly Efficient Maternal-Fetal Zika Virus Transmission in Pregnant Rhesus Macaques

View ORCID ProfileSydney 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. Newman, Michael 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 III, Alice F. Tarantal, Jorge E. Osorio, Shelby L. O’Connor, Thomas C. Friedrich, David H. O’Connor, Thaddeus G. Golos
doi: https://doi.org/10.1101/106674
Sydney M. Nguyen
1Department of Obstetrics and Gynecology, University of Wisconsin-Madison, Madison, USA
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  • ORCID record for Sydney M. Nguyen
Kathleen M. Antony
1Department of Obstetrics and Gynecology, University of Wisconsin-Madison, Madison, USA
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Dawn M. Dudley
2Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, USA
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Sarah Kohn
3Department of Radiology, University of Wisconsin-Madison, Madison, USA
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Heather A. Simmons
5Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison USA
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Bryce Wolfe
2Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, USA
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M. Shahriar Salamat
2Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, USA
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Leandro B. C. Teixeira
10School of Veterinary Medicine, University of Wisconsin-Madison, Madison, USA
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Gregory J. Wiepz
4Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, USA
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Troy H. Thoong
5Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison USA
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Matthew T. Aliota
6Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, USA
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Andrea M. Weiler
5Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison USA
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Gabrielle L. Barry
5Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison USA
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Kim L. Weisgrau
5Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison USA
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Logan J. Vosler
5Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison USA
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Mariel S. Mohns
2Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, USA
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Meghan E. Breitbach
2Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, USA
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Laurel M. Stewart
2Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, USA
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Mustafa N. Rasheed
2Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, USA
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Christina M. Newman
2Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, USA
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Michael E. Graham
2Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, USA
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Oliver E. Wieben
3Department of Radiology, University of Wisconsin-Madison, Madison, USA
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Patrick A. Turski
3Department of Radiology, University of Wisconsin-Madison, Madison, USA
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Kevin M. Johnson
3Department of Radiology, University of Wisconsin-Madison, Madison, USA
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Jennifer Post
5Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison USA
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Jennifer M. Hayes
5Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison USA
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Nancy Schultz-Darken
5Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison USA
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Michele L. Schotzko
5Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison USA
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Josh A. Eudailey
7Department of Pediatrics and Human Vaccine Institute, Duke University Medical Center, Durham, USA
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Sallie R. Permar
7Department of Pediatrics and Human Vaccine Institute, Duke University Medical Center, Durham, USA
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Eva G. Rakasz
5Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison USA
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Emma L. Mohr
8Department of Pediatrics, University of Wisconsin-Madison, Madison, USA
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Saverio Capuano III
5Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison USA
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Alice F. Tarantal
9Departments of Pediatrics and Cell Biology and Human Anatomy, University of California-Davis, California National Primate Research Center, Davis, USA
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Jorge E. Osorio
6Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, USA
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Shelby L. O’Connor
2Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, USA
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Thomas C. Friedrich
5Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison USA
6Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, USA
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David H. O’Connor
2Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, USA
5Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison USA
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Thaddeus G. Golos
1Department of Obstetrics and Gynecology, University of Wisconsin-Madison, Madison, USA
4Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, USA
5Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison USA
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  • For correspondence: golos@primate.wisc.edu
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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.

Author summary Maternal ZIKV infection in pregnancy is associated with severe fetal anomalies, including microcephaly. It has been shown that infection manifests differently in pregnancy than in the non-pregnant state, with prolonged maternal viremia. ZIKV is spread by mosquitos and through sexual contact and since its first detection in early 2015, has become endemic to the Americas. While much has been learned from studying infected human pregnancies, there are still many questions concerning transmission of ZIKV from mother to fetus. Investigating ZIKV infection in non-human primates could help answer these questions due to similarities in the immune system, and the tissues separating the fetus from the mother during pregnancy. Our study serves to model ZIKV transmission in early and late pregnancy, as well as study the effects of this infection on the fetus and mother at these different times in pregnancy. The data collected provides an important insight on ZIKV in pregnancy where the pregnancies have been monitored throughout the entire infection period until term, and suggests that vertical transmission may be very efficient, although severe fetal outcomes are uncommon.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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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. Newman, Michael 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 III, Alice F. Tarantal, Jorge E. Osorio, Shelby L. O’Connor, Thomas C. Friedrich, David H. O’Connor, Thaddeus G. Golos
bioRxiv 106674; doi: https://doi.org/10.1101/106674
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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. Newman, Michael 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 III, Alice F. Tarantal, Jorge E. Osorio, Shelby L. O’Connor, Thomas C. Friedrich, David H. O’Connor, Thaddeus G. Golos
bioRxiv 106674; doi: https://doi.org/10.1101/106674

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