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先天寨卡病毒感染猴仔与登革热免疫力的围产期发育

Neonatal Development in Prenatally Zika Virus-Exposed Infant Macaques with Dengue Immunity.

机构信息

Department of Kinesiology, Occupational Therapy Program, University of Wisconsin-Madison, Madison, WI 53706, USA.

Waisman Center, University of Wisconsin-Madison, Madison, WI 53706, USA.

出版信息

Viruses. 2021 Sep 20;13(9):1878. doi: 10.3390/v13091878.

DOI:10.3390/v13091878
PMID:34578459
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8473338/
Abstract

Infants exposed to Zika virus (ZIKV) prenatally may develop birth defects, developmental deficits, or remain asymptomatic. It is unclear why some infants are more affected than others, although enhancement of maternal ZIKV infection via immunity to an antigenically similar virus, dengue virus (DENV), may play a role. We hypothesized that DENV immunity may worsen prenatal ZIKV infection and developmental deficits in offspring. We utilized a translational macaque model to examine how maternal DENV immunity influences ZIKV-exposed infant macaque neurodevelopment in the first month of life. We inoculated eight macaques with prior DENV infection with ZIKV, five macaques with ZIKV, and four macaques with saline. DENV/ZIKV-exposed infants had significantly worse visual orientation skills than ZIKV-exposed infants whose mothers were DENV-naive, with no differences in motor, sensory or state control development. ZIKV infection characteristics and pregnancy outcomes did not individually differ between dams with and without DENV immunity, but when multiple factors were combined in a multivariate model, maternal DENV immunity combined with ZIKV infection characteristics and pregnancy parameters predicted select developmental outcomes. We demonstrate that maternal DENV immunity exacerbates visual orientation and tracking deficits in ZIKV-exposed infant macaques, suggesting that human studies should evaluate how maternal DENV immunity impacts long-term neurodevelopment.

摘要

先天感染寨卡病毒（ZIKV）的婴儿可能会出现出生缺陷、发育缺陷，或无症状。目前尚不清楚为什么有些婴儿比其他婴儿更容易受到影响，尽管通过对类似抗原的病毒（登革热病毒[DENV]）的免疫作用增强母体 ZIKV 感染可能起作用。我们假设 DENV 免疫可能会加重母体 ZIKV 感染，并导致后代出现发育缺陷。我们利用转化猕猴模型来研究母体 DENV 免疫如何影响 ZIKV 暴露的猕猴幼仔在生命的第一个月的神经发育。我们用 ZIKV 接种了 8 只先前感染过 DENV 的猕猴，用 ZIKV 接种了 5 只猕猴，用生理盐水接种了 4 只猕猴。与母亲未感染 DENV 的 ZIKV 暴露婴儿相比，DENV/ZIKV 暴露婴儿的视觉定向技能明显更差，而运动、感觉或状态控制发育则没有差异。在不考虑 DENV 免疫的情况下，DENV/ZIKV 暴露婴儿的 ZIKV 感染特征和妊娠结局没有差异，但在多变量模型中综合多种因素时，DENV 免疫与 ZIKV 感染特征和妊娠参数相结合可预测特定的发育结局。我们证明，母体 DENV 免疫可加重 ZIKV 暴露的猕猴幼仔的视觉定向和跟踪缺陷，这表明人类研究应评估母体 DENV 免疫对长期神经发育的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec74/8473338/8b6117981243/viruses-13-01878-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec74/8473338/d7d50e5ddd30/viruses-13-01878-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec74/8473338/cad9be670dd8/viruses-13-01878-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec74/8473338/d2682697b428/viruses-13-01878-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec74/8473338/6cdd9a5dd7b5/viruses-13-01878-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec74/8473338/8b6117981243/viruses-13-01878-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec74/8473338/d7d50e5ddd30/viruses-13-01878-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec74/8473338/cad9be670dd8/viruses-13-01878-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec74/8473338/d2682697b428/viruses-13-01878-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec74/8473338/6cdd9a5dd7b5/viruses-13-01878-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec74/8473338/8b6117981243/viruses-13-01878-g005.jpg

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