Consequences of in utero exposure to Zika virus in offspring of AG129 mice.

Consequences of in utero exposure to Zika virus in offspring of AG129 mice.
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DOI:
10.1038/s41598-018-27611-x
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发表时间:
2018-06-20
期刊:
影响因子:
4.6
通讯作者:
Morrey JD
Morrey JD
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Julander JG;Siddharthan V;Park AH;Preston E;Mathur P;Bertolio M;Wang H;Zukor K;Van Wettere AJ;Sinex DG;Morrey JD

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寨卡病毒(ZIKV)是一种常见的寨卡病毒。本研究的目的是鉴定在子宫内暴露于ZIKV的幼崽中的疾病表型。交配后7.5天(dpc)用ZIKV腹膜内感染雌性干扰素-α/β,-γ受体敲除小鼠(AG 129)。在妊娠期间的不同时间,在部分(但不是全部)母体和胎儿组织中检测到病毒RNA、抗原和感染性病毒。感染母鼠的胎儿有显著的宫内生长受限(IUGR),这在接近分娩的母鼠中更为明显。与年龄匹配的对照组相比,感染母鼠出生的幼崽明显较小,头骨长度明显缩短,这是通过卡尺测量和显微CT分析确定的。然而,出生后暴露幼崽的生长率与假暴露后代相似。出生后,在感染母鼠的幼仔中检测到病毒RNA。在子宫内暴露于ZIKV的新生儿中观察到较低的存活率。超过50%的死亡率,归因于ZIKV感染的后果,发生在出生后的幼崽感染的母鼠。在子宫内暴露于病毒的一些动物中观察到一过性听力损失。使用转轮或病毒性轻瘫评分测定法未检测到运动缺陷或认知缺陷。后代的缺陷包括较小的尺寸,较短的头骨长度和新生儿死亡率增加,而我们可以检测到的唯一功能缺陷是短暂性听力损失的发生率较低。
Zika virus (ZIKV) can cause various diseases in offspring after congenital infection. The purpose of this study was to identify disease phenotypes in pups exposed to ZIKV in utero. Female interferon-α/β, -γ receptor knockout mice (AG129) were infected intraperitoneally with ZIKV 7.5 days’ post coitus (dpc). Viral RNA, antigen and infectious virus were detected in some, but not all, maternal and fetal tissues at various times during gestation. Fetuses of infected dams had significant intrauterine growth restriction (IUGR), which was more pronounced as females neared parturition. Pups born to infected dams were significantly smaller and had significantly shortened skull lengths, as determined by measurement with a caliper and by micro-CT analysis, as compared with age-matched controls. Growth rates of exposed pups after birth, however, was similar to sham-exposed offspring. Viral RNA was detected in pups of infected dams after birth. A lower survival rate was observed in neonates exposed to ZIKV in utero. A mortality rate of over 50%, attributed to consequences of ZIKV infection, occurred after birth in pups born to infected dams. A transient hearing loss was observed in some animals exposed to virus in utero. No motor deficits or cognitive deficits were detected using running wheel or viral paresis scoring assays. Abnormalities in offspring included smaller size, shorter skull length and increased neonatal mortality, while the only functional deficit we could detect was a low incidence of transient hearing loss.
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影响因子: 39.2
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发表时间: 2016-12-15
期刊: The New England journal of medicine
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