Highly Efficient Maternal-Fetal Zika Virus Transmission in Pregnant Rhesus Macaques
Authors: Nguyen Sydney M. , Antony Kathleen M. , Dudley Dawn M. , Kohn Sarah , Simmons Heather A. , Wolfe Bryce , Shahriar Salamat M. , Teixeira Leandro B. C. , Wiepz Gregory J. , Thoong Troy H. , Aliota Matthew T. , Weiler Andrea M. , Barry Gabrielle L. , Weisgrau Kim L. , Vosler Logan J. , Mohns Mariel S. , Breitbach Meghan E. , Stewart Laurel M. , Rasheed Mustafa N. , Newman Christina M. , Graham Michael E. , Wieben Oliver E. , Turski Patrick A. , Johnson Kevin M. , Post Jennifer , Hayes Jennifer M. , Schultz-Darken Nancy , Schotzko Michele L. , Eudailey Josh A. , Permar Sallie R. , Rakasz Eva G. , Mohr Emma L. , Capuano Saverio , Tarantal Alice F. , Osorio Jorge E. , O’Connor Shelby L. , Friedrich Thomas C. , O’Connor David H. , Golos Thaddeus G. 
Published: February 2017

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.