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

PLoS Pathogens

Gregory J. Wiepz¹  Sydney M. Nguyen²  Kathleen M. Antony²  Jorge E. Osorio³  Matthew T. Aliota³  David H. O’Connor³  Laurel M. Stewart⁴  M. Shahriar Salamat⁴  Shelby L. O’Connor⁴  Dawn M. Dudley⁴  Christina M. Newman⁴  Meghan E. Breitbach⁴  Thaddeus G. Golos⁴  Michael E. Graham⁴  Mariel S. Mohns⁴  Bryce Wolfe⁴  Mustafa N. Rasheed⁴  Sallie R. Permar⁵  Josh A. Eudailey⁵  Emma L. Mohr⁶  Sarah Kohn⁷  Oliver E. Wieben⁷  Kevin M. Johnson⁷  Patrick A. Turski⁷  Alice F. Tarantal⁸  Leandro B. C. Teixeira⁹  Jennifer Post^1,10  Thomas C. Friedrich^1,10  Heather A. Simmons^1,10  Andrea M. Weiler^1,10  Michele L. Schotzko^1,10  Troy H. Thoong^1,10  Gabrielle L. Barry^1,10  Eva G. Rakasz^1,10  Logan J. Vosler^1,10  Kim L. Weisgrau^1,10  Saverio Capuano III^1,10  Nancy Schultz-Darken^1,10  Jennifer M. Hayes^1,10 

[1] Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin, United States of America;Department of Obstetrics and Gynecology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America;Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States of America;Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America;Department of Pediatrics and Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, United States of America;Department of Pediatrics, University of Wisconsin-Madison, Madison, Wisconsin, United States of America;Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America;Departments of Pediatrics and Cell Biology and Human Anatomy, University of California-Davis, California National Primate Research Center, Davis, California, United States of America;School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America;Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America

关键词: Macaque;    Zika virus;    Pregnancy;    Viremia;    Amniotic fluid;    Rhesus monkeys;    Fetuses;    Magnetic resonance imaging;   

DOI  :  10.1371/journal.ppat.1006378

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY