RT Journal Article SR Electronic T1 Highly Efficient Maternal-Fetal Zika Virus Transmission in Pregnant Rhesus Macaques JF bioRxiv FD Cold Spring Harbor Laboratory SP 106674 DO 10.1101/106674 A1 Sydney M. Nguyen A1 Kathleen M. Antony A1 Dawn M. Dudley A1 Sarah Kohn A1 Heather A. Simmons A1 Bryce Wolfe A1 M. Shahriar Salamat A1 Leandro B. C. Teixeira A1 Gregory J. Wiepz A1 Troy H. Thoong A1 Matthew T. Aliota A1 Andrea M. Weiler A1 Gabrielle L. Barry A1 Kim L. Weisgrau A1 Logan J. Vosler A1 Mariel S. Mohns A1 Meghan E. Breitbach A1 Laurel M. Stewart A1 Mustafa N. Rasheed A1 Christina M. Newman A1 Michael E. Graham A1 Oliver E. Wieben A1 Patrick A. Turski A1 Kevin M. Johnson A1 Jennifer Post A1 Jennifer M. Hayes A1 Nancy Schultz-Darken A1 Michele L. Schotzko A1 Josh A. Eudailey A1 Sallie R. Permar A1 Eva G. Rakasz A1 Emma L. Mohr A1 Saverio Capuano III A1 Alice F. Tarantal A1 Jorge E. Osorio A1 Shelby L. O’Connor A1 Thomas C. Friedrich A1 David H. O’Connor A1 Thaddeus G. Golos YR 2017 UL http://biorxiv.org/content/early/2017/05/11/106674.abstract AB 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.