Department of Psychology, University of California, Davis, Davis, CA 95616, USA.
California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA.
Sci Transl Med. 2023 Oct 25;15(719):eadh0043. doi: 10.1126/scitranslmed.adh0043.
There is enormous variation in the extent to which fetal Zika virus (fZIKV) infection affects the developing brain. Despite the neural consequences of fZIKV infection observed in people and animal models, many open questions about the relationship between infection dynamics and fetal and infant development remain. To further understand how ZIKV affects the developing nervous system and the behavioral consequences of prenatal infection, we adopted a nonhuman primate model of fZIKV infection in which we inoculated pregnant rhesus macaques and their fetuses with ZIKV in the early second trimester of fetal development. We then tracked their health across gestation and characterized infant development across the first month of life. ZIKV-infected pregnant mothers had long periods of viremia and mild changes to their hematological profiles. ZIKV RNA concentrations, an indicator of infection magnitude, were higher in mothers whose fetuses were male, and the magnitude of ZIKV RNA in the mothers' plasma or amniotic fluid predicted infant outcomes. The magnitude of ZIKV RNA was negatively associated with infant growth across the first month of life, affecting males' growth more than females' growth, although for most metrics, both males and females evidenced slower growth rates as compared with control animals whose mothers were not ZIKV inoculated. Compared with control infants, fZIKV infants also spent more time with their mothers during the first month of life, a social behavior difference that may have long-lasting consequences on psychosocial development during childhood.
胎儿寨卡病毒 (fZIKV) 感染对大脑发育的影响程度存在巨大差异。尽管在人和动物模型中观察到了 fZIKV 感染的神经后果，但关于感染动态与胎儿和婴儿发育之间的关系仍存在许多悬而未决的问题。为了进一步了解寨卡病毒如何影响发育中的神经系统以及产前感染的行为后果，我们采用了一种非人类灵长类动物模型来感染 fZIKV，即在胎儿发育的第二个月早期向怀孕的恒河猴及其胎儿接种寨卡病毒。然后，我们跟踪了它们在妊娠期的健康状况，并在生命的第一个月内描述了婴儿的发育情况。感染寨卡病毒的孕妇会长期出现病毒血症和轻微的血液学特征变化。母体血浆或羊水的 ZIKV RNA 浓度，这是感染程度的一个指标，在胎儿为男性的母体中更高，而母体血浆或羊水的 ZIKV RNA 浓度则可以预测婴儿的结局。ZIKV RNA 的浓度与婴儿在生命的第一个月内的生长呈负相关，对男性的生长影响大于对女性的生长，尽管对于大多数指标，与未接种 ZIKV 的母亲的对照动物相比，男性和女性的生长速度都较慢。与对照婴儿相比，fZIKV 婴儿在生命的第一个月也与母亲在一起的时间更多，这种社交行为差异可能对儿童期的社会心理发展产生持久影响。
