Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington.
Center for Innate Immunity and Immune Disease, University of Washington, Seattle, Washington.
Viral Immunol. 2020 Jan/Feb;33(1):22-37. doi: 10.1089/vim.2019.0082. Epub 2019 Nov 5.
Zika virus (ZIKV) is a mosquito-transmitted flavivirus that caused a public health emergency in the Americas when an outbreak in Brazil became linked to congenital microcephaly. Understanding how ZIKV could evade the innate immune defenses of the mother, placenta, and fetus has become central to determining how the virus can traffic into the fetal brain. ZIKV, like other flaviviruses, evades host innate immune responses by leveraging viral proteins and other processes that occur during viral replication to allow spread to the placenta. Within the placenta, there are diverse cell types with coreceptors for ZIKV entry, creating an opportunity for the virus to establish a reservoir for replication and infect the fetus. The fetal brain is vulnerable to ZIKV, particularly during the first trimester, when it is beginning a dynamic process, to form highly complex and specialized regions orchestrated by neuroprogenitor cells. In this review, we provide a conceptual framework to understand the different routes for viral trafficking into the fetal brain and the eye, which are most likely to occur early and later in pregnancy. Based on the injury profile in human and nonhuman primates, ZIKV entry into the fetal brain likely occurs across both the blood/cerebrospinal fluid barrier in the choroid plexus and the blood/brain barrier. ZIKV can also enter the eye by trafficking across the blood/retinal barrier. Ultimately, the efficient escape of innate immune defenses by ZIKV is a key factor leading to viral infection. However, the host immune response against ZIKV can lead to injury and perturbations in developmental programs that drive cellular division, migration, and brain growth. The combined effect of innate immune evasion to facilitate viral propagation and the maternal/placental/fetal immune response to control the infection will determine the extent to which ZIKV can injure the fetal brain.
寨卡病毒（ZIKV）是一种通过蚊子传播的黄病毒，当巴西的一次疫情与先天性小头畸形有关时，它引发了美洲的公共卫生紧急事件。了解寨卡病毒如何逃避母亲、胎盘和胎儿的先天免疫防御，已成为确定病毒如何进入胎儿大脑的关键。寨卡病毒与其他黄病毒一样，通过利用病毒蛋白和病毒复制过程中的其他过程来逃避宿主先天免疫反应，从而允许病毒传播到胎盘。在胎盘内，有多种具有寨卡病毒进入核心受体的细胞类型，为病毒建立复制库并感染胎儿创造了机会。胎儿大脑容易受到寨卡病毒的感染，尤其是在妊娠的头三个月，此时大脑正在开始一个动态的过程，形成由神经祖细胞协调的高度复杂和专门的区域。在这篇综述中，我们提供了一个概念框架，以了解病毒进入胎儿大脑和眼睛的不同途径，这些途径很可能在妊娠早期和晚期发生。基于人类和非人灵长类动物的损伤谱，寨卡病毒进入胎儿大脑的途径可能包括脉络丛的血脑屏障和血脑屏障。寨卡病毒也可以通过穿越血视网膜屏障进入眼睛。最终，寨卡病毒对先天免疫防御的有效逃避是导致病毒感染的关键因素。然而，宿主对寨卡病毒的免疫反应会导致细胞分裂、迁移和大脑生长的发育程序受到损伤和干扰。先天免疫逃避以促进病毒繁殖的作用，以及母体/胎盘/胎儿免疫反应以控制感染的作用，将决定寨卡病毒对胎儿大脑造成损伤的程度。
