Nguyen Sydney M, Antony Kathleen M, Dudley Dawn M, Kohn Sarah, Simmons Heather A, Wolfe Bryce, Salamat M Shahriar, 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
Department of Obstetrics and Gynecology, 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.
PLoS Pathog. 2017 May 25;13(5):e1006378. doi: 10.1371/journal.ppat.1006378. eCollection 2017 May.
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.
感染寨卡病毒(ZIKV)与人类先天性胎儿异常有关。为了在非人灵长类动物中模拟胎儿结局,我们对4只怀孕的恒河猴皮下注射了亚洲谱系的寨卡病毒。在之前一项与本报告同期进行的研究中,非怀孕动物在10 - 12天内清除病毒血症,但在本次研究的4次怀孕中,有3次母体病毒血症持续时间延长。通过超声测量头围来确定妊娠最后一个月胎儿头部生长速度,与每个胎儿的双顶径和股骨长度相比有所下降,不过均在正常范围内。在足月剖宫产时,在所有4只胎儿的组织中均检测到寨卡病毒RNA。在所有妊娠中,在母胎界面(蜕膜、胎盘、胎膜)、各种胎儿组织以及胎儿视网膜、脉络膜和视神经(仅孕早期感染)中均存在嗜中性粒细胞浸润。在这个灵长类动物模型中一致的垂直传播可能为评估危险因素和测试中断胎儿感染的治疗干预措施提供一个平台。这些结果还可能表明,人类妊娠中母胎寨卡病毒传播可能比目前所认识的更为频繁。