Zika virus (ZIKV) infection is associated with congenital defects and pregnancy loss. Here, we found that 26% of nonhuman primates infected with Asian/American ZIKV in early gestation experienced fetal demise later in pregnancy despite showing few clinical signs of infection. Pregnancy loss due to asymptomatic ZIKV infection may therefore be a common but under-recognized adverse outcome related to maternal ZIKV infection.
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We thank the Veterinary Services, Colony Management, Scientific Protocol Implementation, and Pathology Services staff at the WNPRC for their contribution to this study. We thank M. Harke, K. Brunner, T. Frost, M. Schotzko, W. Newton, K. Antony, S. Kohn, C. Newman, L. Stewart, M. Koenig, M. Breitbach, and M. Mohns for technical assistance and for monitoring the ZIKV-infected pregnant animals at WNPRC. We thank J. Eickhoff for help with statistical analysis. We thank T. Morgan for help with interpreting pathology. Studies at WNPRC were supported by DHHS/PHS/NIH R01Al116382-01A1 to D.H.O. and by the Pediatric Infectious Diseases Society to E.L.M. We thank E. Kallas for providing information on 2016 live-birth rates in Brazil. This work was also supported in part by the Office of Research Infrastructure Programs/OD grant (P51OD011106) awarded to WNPRC, Madison–Wisconsin. This research was conducted in part at a facility constructed with support from Research Facilities Improvement Program grants RR15459-01 and RR020141-01. The studies at CNPRC were supported by a CNPRC pilot research grant, 1R21AI129479-01 (K.K.V.R.), the Office of Research Infrastructure Programs/OD (P51OD011107) (CNPRC), FDA contract HHSF223201610542P (L.L.C.) and start-up funds from the Pathology, Microbiology and Immunology Department to L.L.C. We thank V. Bakula, I. Cazares, M. Christensen, C. Cruzen, A. Gibbons, D. Lemos, A. Singapuri, J. Usachenko, W. von Morgenland, J. Watanabe, J. Yee, A. Murphy, and the staff of Clinical Labs, Veterinary and Colony Research Services for technical assistance. Work at the ONPRC was supported by the National Institutes of Health Office of Research Infrastructure Programs grant (P51OD011092) to ONPRC and R21HD091032 to D.N.S. We thank L. Drew Martin, B. Dozier and N. Sternberger for their veterinary expertise, and the dedicated staff in the ONPRC Department of Comparative Medicine for assistance with animal care. The studies at Tulane National Primate Research Center (TNPRC) were supported by NIH grant R01 AI099795-05 to X.W. and by the National Institutes of Health Office of Research Infrastructure Program grant (P51OD011104) to TNPRC. We thank F. Schiro, R. Blair, and P. Aye for technical assistance. At WaNPRC, the work was primarily supported by generous private philanthropic gifts, including those from five donors from Florida who wish to remain anonymous. Further support was obtained from the University of Washington Department of Obstetrics & Gynecology, the Seattle Children’s Research Institute, and National Institutes of Health grants R01AI100989 (L.R. and K.A.W.), AI083019 (M.G.), and AI104002 (M.G.). The National Institutes of Health Office of Research Infrastructure Programs (P51 OD010425) also supported this project. We thank J. Ogle, W. Lee, and J. Thiel for technical assistance in monitoring the animals. Work at SNPRC was supported by NIH grants R01HL105704 and R21AI129455 (C.Y.C.), National Institutes of Health Office of Research Infrastructure Programs grant P51 ODOD011133 to SNPRC, and the Texas Biomedical Research Institute. We thank D. Layne-Colon for marmoset pregnancy management, ultrasonography, and collection and processing of placental and fetal material. We also thank S. Davis for technical support; M. Suter for guidance in the placental studies and analysis; and X. de Lamballerie (European Virus Archive) and B. Russell (CDC) for providing ZIKV strains.
The authors declare no competing interests.
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Dudley, D.M., Van Rompay, K.K., Coffey, L.L. et al. Miscarriage and stillbirth following maternal Zika virus infection in nonhuman primates. Nat Med 24, 1104–1107 (2018). https://doi.org/10.1038/s41591-018-0088-5
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