Correlation between Apoptosis and in Situ Immune Response in Fatal Cases of Microcephaly Caused by Zika Virus
Correlation between Apoptosis and in Situ Immune Response in Fatal Cases of Microcephaly Caused by Zika Virus
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DOI：
10.1016/j.ajpat
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发表时间：
2018-11-01
影响因子：
6
通讯作者：
Vasconcelos, Pedro F. C.
中科院分区：
文献类型：
--
作者：
de Sousa, Jorge R.;Azevedo, Raimunda S. S.;Vasconcelos, Pedro F. C.
寨卡病毒（ZIKV）是一种单股正义RNA黄病毒，其基因组长度约为10.7 Kb。虽然属于外在和内在途径的促炎和抗炎细胞因子和凋亡标志物被认为参与ZIKV诱导的小头畸形的致命病例，但它们的确切作用和关联尚不清楚。为了解决这个问题，从10个个体中收集脑组织样品，其中5个被诊断为ZIKV阳性伴小头畸形，另外5个是黄病毒阴性对照，由于其他原因死亡。对来自致死性小头畸形病例的材料进行检查，发现大脑皮质病变、水肿、血管增生、神经元坏死、神经胶质增生、神经元吞噬、钙化、细胞凋亡和神经元丢失。ZIKV阳性病例和对照组之间神经实质中各种凋亡标志物的表达不同，包括FasL、FAS、BAX、BCL 2和半胱天冬酶3。对1型和2型辅助性T细胞细胞因子的进一步研究证实，在致死性ZIKV相关小头畸形病例中有更大的抗炎反应。最后，对肿瘤坏死因子-α、IL-1 β、IL-4、IL-10、转化生长因子-β和IL-33表达与各种凋亡标志物之间的线性相关性的分析表明，免疫应答可能与在ZIKV诱导的小头畸形中观察到的凋亡现象相关。
Zika virus (ZIKV) is a single-stranded positive-sense RNA flavivirus that possesses a genome approximately 10.7 Kb in length. Although pro-inflammatory and anti-inflammatory cytokines and apoptotic markers belonging to the extrinsic and intrinsic pathways are suggested to be involved in fatal cases of ZIKV-induced microcephaly, their exact roles and associations are unclear. To address this, brain tissue samples were collected from 10 individuals, five of whom were diagnosed as ZIKV positive with microcephaly and a further five were flavivirus-negative controls that died because of other causes. Examination of material from the fatal cases of microcephaly revealed lesions in the cerebral cortex, edema, vascular proliferation, neuronal necrosis, gliosis, neuronophagy, calcifications, apoptosis, and neuron loss. The expression of various apoptosis markers in the neural parenchyma, including FasL, FAS, BAX, BCL2, and caspase 3 differed between ZIKV-positive cases and controls. Further investigation of type 1 and 2 helper T-cell cytokines confirmed a greater anti-inflammatory response in fatal ZIKV-associated microcephaly cases. Finally, an analysis of the linear correlation between tumor necrosis factor-alpha, IL-1 beta, IL-4, IL-10, transforming growth factor-beta, and IL-33 expression and various apoptotic markers suggested that the immune response may be associated with the apoptotic phenomenon observed in ZIKV-induced microcephaly.