Infect Genet Evol:寨卡病毒通过负面影响颅神经嵴发育诱导异常颅骨成骨

2019-01-25 MedSci MedSci原创

妊娠期间寨卡病毒(ZIKV)感染被认为通过神经发生期间神经系统的直接损伤与出生缺陷相关。然而,在这项研究中,我们的数据显示ZIKV感染显著抑制了鸡胚胎中的Safranin O / Fast Green和茜素红染色显示的颅骨成骨,这提供了由ZIKV引起的颅面骨畸形的另一种可能性。通过免疫荧光染色和电子显微镜,我们证实了鸡胚神经管和神经嵴部位的ZIKV感染。接下来,体内(鸡胚)和体外[神经嵴细胞(NC

妊娠期间寨卡病毒(ZIKV)感染被认为通过神经发生期间神经系统的直接损伤与出生缺陷相关。然而,在这项研究中,我们的数据显示ZIKV感染显著抑制了鸡胚胎中的Safranin O / Fast Green和茜素红染色显示的颅骨成骨,这提供了由ZIKV引起的颅面骨畸形的另一种可能性。

通过免疫荧光染色和电子显微镜,我们证实了鸡胚神经管和神经嵴部位的ZIKV感染。接下来,体内(鸡胚)和体外[神经嵴细胞(NCC)的原代培养物] ZIKV和HNK-1双重免疫荧光染色证明ZIKV感染抑制迁移性NCC的产生。由ZIKV感染的HH10鸡胚中AP-2α-和Pax7-阳性NCC的减少证实,在迁移过程中也发生了颅NCC的异常发育。整体原位杂交证明,在ZIKV感染的HH10鸡胚中,钙粘蛋白6B表达升高并且Slug,FoxD3和BMP4 / Msx1表达降低,这意味着神经嵴产生的上皮-间质转化(EMT)被ZIKV感染阻断。此外,体内和体外pHIS3和Pax7双重免疫荧光染色显示ZCCV感染抑制NCC增殖。HH10鸡胚胎中C-caspase-3和AP-2α双重免疫荧光染色和Western印迹显示ZIKV感染后NCC凋亡增加。最后,电子显微镜显示在ZIKV感染的胚胎中有多个自噬体,Western印迹和LC3B免疫荧光染色证明自噬相关基因被ZIKV感染激活。

总之,我们的数据首次表明,胚胎发生过程中的ZIKV感染可能干扰颅神经嵴发育,进而导致颅骨成骨异常。我们的结果为ZIKV感染引起的脑畸形提供了新的见解。

原始出处:

Yan Y1, Zhang XT, et al. Zika virus induces abnormal cranial osteogenesis by negatively affecting cranial neural crest development. Infect Genet Evol. 2019 Jan 18. pii: S1567-1348(18)30781-0. doi: 10.1016/j.meegid.2019.01.023.

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    2019-06-01 zhaojie88
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    2019-10-13 智慧医人
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    2019-01-27 neurowu
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    2019-01-27 zhaojie88
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