Zika virus impairs the development of blood vessels in a mouse model of congenital infection.
Zika virus impairs the development of blood vessels in a mouse model of congenital infection.
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DOI：
10.1038/s41598-018-31149-3
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发表时间：
2018-08-24
影响因子：
4.6
通讯作者：
Molnár Z
中科院分区：
文献类型：
--
作者：
Garcez PP;Stolp HB;Sravanam S;Christoff RR;Ferreira JCCG;Dias AA;Pezzuto P;Higa LM;Barbeito-Andrés J;Ferreira RO;Andrade CBV;Siqueira M;Santos TMP;Drumond J;Hoerder-Suabedissen A;de Lima CVF;Tovar-Moll F;Lopes RT;Fragel-Madeira L;Lent R;Ortiga-Carvalho TM;Stipursky J;Bellio M;Tanuri A;Molnár Z
寨卡病毒（ZIKV）与大脑发育异常有关，如原发性小头畸形，大脑生长严重减少。在这里，我们在体内证明了先天性ZIKV感染对血管发育的影响，血管发育是器官发生的关键步骤。在胚胎第（E）12.5天将ZIKV静脉内注射到妊娠的2型干扰素（IFN）缺陷小鼠中。在E15.5和出生后第2天（P）收集胚胎。在E15.5时，皮质祖细胞和神经元标志物的免疫组织化学显示，由于ZIKV感染，两个群体都减少。使用共聚焦3D成像，我们发现与E15.5的模拟相比，ZIKV感染的脑切片显示出脉管系统密度和血管分支的减少;总之，皮质血管在感染的组织中呈现出相对不成熟的模式。这些受损的血管模式在胎盘和视网膜中也很明显。此外，蛋白质组学分析表明，与对照组相比，受感染的大脑中的血管生成蛋白被解除管制。在P2时，与模拟感染动物相比，皮质大小和脑重量减少。总之，我们的结果表明，ZIKV在发育期间除了神经发生之外还损害血管生成。血管系统的缺陷限制了一般的脑生长，但也可以直接调节神经发生。
Zika virus (ZIKV) is associated with brain development abnormalities such as primary microcephaly, a severe reduction in brain growth. Here we demonstrated in vivo the impact of congenital ZIKV infection in blood vessel development, a crucial step in organogenesis. ZIKV was injected intravenously in the pregnant type 2 interferon (IFN)-deficient mouse at embryonic day (E) 12.5. The embryos were collected at E15.5 and postnatal day (P)2. Immunohistochemistry for cortical progenitors and neuronal markers at E15.5 showed the reduction of both populations as a result of ZIKV infection. Using confocal 3D imaging, we found that ZIKV infected brain sections displayed a reduction in the vasculature density and vessel branching compared to mocks at E15.5; altogether, cortical vessels presented a comparatively immature pattern in the infected tissue. These impaired vascular patterns were also apparent in the placenta and retina. Moreover, proteomic analysis has shown that angiogenesis proteins are deregulated in the infected brains compared to controls. At P2, the cortical size and brain weight were reduced in comparison to mock-infected animals. In sum, our results indicate that ZIKV impairs angiogenesis in addition to neurogenesis during development. The vasculature defects represent a limitation for general brain growth but also could regulate neurogenesis directly.
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影响因子：
5.3
作者：
Logsdon EA;Finley SD;Popel AS;Mac Gabhann F
通讯作者：
Mac Gabhann F
影响因子：
6.4
作者：
Mladinich MC;Schwedes J;Mackow ER
通讯作者：
Mackow ER
小鼠的慢性蛋白质限制会影响胎儿生长前的胎盘功能和母亲体重。
影响因子：
3.7
作者：
Gonzalez PN;Gasperowicz M;Barbeito-Andrés J;Klenin N;Cross JC;Hallgrímsson B
通讯作者：
Hallgrímsson B
影响因子：
23.9
作者：
Nowakowski TJ;Pollen AA;Di Lullo E;Sandoval-Espinosa C;Bershteyn M;Kriegstein AR
通讯作者：
Kriegstein AR
影响因子：
11.1
作者：
Cui L;Zou P;Chen E;Yao H;Zheng H;Wang Q;Zhu JN;Jiang S;Lu L;Zhang J
通讯作者：
Zhang J