Department of Genetics, Institute of Biosciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
National Institute of Population Medical Genetics (INAGEMP), Porto Alegre, Brazil.
Neuroimmunomodulation. 2018;25(5-6):320-327. doi: 10.1159/000495660. Epub 2019 Jan 10.
The recent outbreak of the Zika virus (ZIKV) and the discovery that perinatal Zika exposure can lead to the Congenital Zika Syndrome has promoted a call for prevention measures. Due to the increased number of babies born with microcephaly, structural brain abnormalities, and neurological alterations in regions affected by ZIKV, investigations were carried out in order to better understand this process. The maternal immune system directly influences the fetal central nervous system, and complications during pregnancy have been associated with neurodevelopmental disorders. Autism spectrum disorder (ASD), a neurodevelopmental disorder commonly manifested in the first years of life, is a disease with multifactorial etiology and is manifested typically by social and communication impairments, as well as stereotyped behaviors. Brain abnormalities, including both anatomically and functionally, can be observed in this disorder, suggesting delays in neuronal maturation and altered brain connectivity. It is known that some viral congenital infections, such as rubella, and cytomegalovirus can interfere with brain development, being associated with brain calcification, microcephaly, and ASD. Here, we reviewed a range of studies evaluating the aspects concerning brain development, immunological status during pregnancy, and neuroimmunomodulation in congenital viral infections, and we discuss if the fetal brain infection caused by ZIKV could predispose to ASD. Finally, we suggest a mechanism encompassing neurological and immunological pathways that could play a role in the development of ASD in infants after ZIKV infection in pregnancy.
最近寨卡病毒（ZIKV）的爆发以及围产期寨卡病毒暴露可导致先天性寨卡综合征的发现，促使人们呼吁采取预防措施。由于患有小头畸形、结构脑异常和受 ZIKV 影响的区域出现神经改变的婴儿数量增加，因此进行了相关研究以更好地了解这一过程。母体免疫系统直接影响胎儿中枢神经系统，而怀孕期间的并发症与神经发育障碍有关。自闭症谱系障碍（ASD）是一种常见于生命早期的神经发育障碍，是一种具有多种病因的疾病，其典型表现为社交和沟通障碍以及刻板行为。在这种疾病中可以观察到大脑异常，包括解剖和功能方面的异常，这表明神经元成熟延迟和大脑连接改变。已知一些先天性病毒感染，如风疹和巨细胞病毒会干扰大脑发育，与脑钙化、小头畸形和 ASD 有关。在这里，我们回顾了一系列评估与大脑发育、妊娠期间免疫状态和先天性病毒感染的神经免疫调节相关的研究，并讨论了 ZIKV 引起的胎儿大脑感染是否会导致 ASD。最后，我们提出了一个包含神经和免疫途径的机制，该机制可能在妊娠期间 ZIKV 感染后婴儿的 ASD 发展中发挥作用。
