Developmental Biology Program, Sloan Kettering Institute for Cancer Research, New York, NY, USA.
The Center for Stem Cell Biology, Sloan Kettering Institute for Cancer Research, New York, NY, USA.
Nat Rev Immunol. 2021 Jul;21(7):441-453. doi: 10.1038/s41577-020-00474-y. Epub 2021 Jan 4.
Advancements in human pluripotent stem cell technology offer a unique opportunity for the neuroimmunology field to study host-virus interactions directly in disease-relevant cells of the human central nervous system (CNS). Viral encephalitis is most commonly caused by herpesviruses, arboviruses and enteroviruses targeting distinct CNS cell types and often leading to severe neurological damage with poor clinical outcomes. Furthermore, different neurotropic viruses will affect the CNS at distinct developmental stages, from early prenatal brain development to the aged brain. With the unique flexibility and scalability of human pluripotent stem cell technology, it is now possible to examine the molecular mechanisms underlying acute infection and latency, determine which CNS subpopulations are specifically infected, study temporal aspects of viral susceptibility, perform high-throughput chemical or genetic screens for viral restriction factors and explore complex cell-non-autonomous disease mechanisms. Therefore, human pluripotent stem cell technology has the potential to address key unanswered questions about antiviral immunity in the CNS, including emerging questions on the potential CNS tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
人类多能干细胞技术的进步为神经免疫学界提供了一个独特的机会，可以直接在人类中枢神经系统（CNS）中与疾病相关的细胞中研究宿主-病毒相互作用。病毒性脑炎最常见的病因是疱疹病毒、虫媒病毒和肠道病毒，它们针对不同的 CNS 细胞类型，通常导致严重的神经损伤和不良的临床结果。此外，不同的神经嗜性病毒会在不同的发育阶段影响中枢神经系统，从早期产前脑发育到老年脑。利用人类多能干细胞技术独特的灵活性和可扩展性，现在可以研究急性感染和潜伏的分子机制，确定哪些 CNS 亚群受到特异性感染，研究病毒易感性的时间方面，进行高通量化学或遗传筛选以寻找病毒限制因子，并探索复杂的细胞非自主性疾病机制。因此，人类多能干细胞技术有可能解决中枢神经系统抗病毒免疫方面的一些关键未解问题，包括严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）在中枢神经系统中潜在嗜性的新出现问题。
