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寨卡病毒的非洲株在猪胎儿传播模型中比亚洲株引起更严重的感染。

The African strain of Zika virus causes more severe infection than Asian strain in a porcine fetal transmission model.

机构信息

a Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac), University of Saskatchewan , Saskatoon , Canada.

b School of Public Health, University of Saskatchewan , Saskatoon , Canada.

出版信息

Emerg Microbes Infect. 2019;8(1):1098-1107. doi: 10.1080/22221751.2019.1644967.

Abstract

Studies in mice showed that African Zika virus (ZIKV) strains cause more damage in embryos. These studies, however, were limited to the mouse-adapted African MR766 strain or infection at early gestation. Here, we compared infection of Asian and African strains in the fetal pig model at midgestation. Both strains caused fetal infection. ZIKV was detected in placenta, amniotic membrane, amniotic fluid, fetal blood, and brain. The African strain produced more vigorous infection as represented by more efficient virus transmission between siblings, and higher viral loads in fetal organs and membranes. Infection with both strains was associated with reduced fetal brain weight and increased number of placental CD163-positive cells, as well as elevated interferon alpha and cortisol levels. This is the first large animal model study which demonstrated that African strain of ZIKV, with no passage history in experimental animals, can cause persistent infection in fetuses and fetal membranes at midgestation. Our studies also suggest that similar to Asian strains, ZIKV of African lineage might cause silent pathology which is difficult to identify in deceptively healthy fetuses. The findings emphasize the need for further studies to highlight the impact of ZIKV heterogeneity on infection outcomes during pregnancy.

摘要

在老鼠身上的研究表明,非洲寨卡病毒(ZIKV)株在胚胎中引起更多的损害。然而,这些研究仅限于适应于老鼠的非洲 MR766 株或在妊娠早期的感染。在这里,我们比较了中孕期胎儿猪模型中感染的亚洲和非洲株。两种株都引起了胎儿感染。ZIKV 被检测到在胎盘、羊膜、羊水、胎儿血液和大脑中。非洲株产生了更强烈的感染,表现为兄弟姐妹之间更有效的病毒传播,以及胎儿器官和膜中的更高病毒载量。两种株的感染都与胎儿脑重减轻和胎盘 CD163 阳性细胞增多有关,以及干扰素 α 和皮质醇水平升高。这是第一个大型动物模型研究,表明没有在实验动物中经过传代的非洲 ZIKV 株,可在妊娠中期引起胎儿和胎膜的持续感染。我们的研究还表明,类似于亚洲株,非洲谱系的 ZIKV 可能会引起难以在看似健康的胎儿中识别的沉默性病理。这些发现强调了需要进一步研究来强调寨卡病毒异质性对妊娠期间感染结果的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6291/6711198/1bbb6874634d/TEMI_A_1644967_F0001_OC.jpg

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