Center for Neuroimmunology & Neuroinfectious Diseases, Departments of Medicine, Pathology & Immunology, Neurosciences, Washington University School of Medicine, St. Louis, Missouri, USA.
Glia. 2023 Apr;71(4):803-818. doi: 10.1002/glia.24294. Epub 2022 Nov 5.
Many viral infections cause acute and chronic neurologic diseases which can lead to degeneration of cortical functions. While neurotropic viruses that gain access to the central nervous system (CNS) may induce brain injury directly via infection of neurons or their supporting cells, they also alter brain function via indirect neuroimmune mechanisms that may disrupt the blood-brain barrier (BBB), eliminate synapses, and generate neurotoxic astrocytes and microglia that prevent recovery of neuronal circuits. Non-neuroinvasive, neurovirulent viruses may also trigger aberrant responses in glial cells, including those that interfere with motor and sensory behaviors, encoding of memories and executive function. Increasing evidence from human and animal studies indicate that neuroprotective antiviral responses that amplify levels of innate immune molecules dysregulate normal neuroimmune processes, even in the absence of neuroinvasion, which may persist after virus is cleared. In this review, we discuss how select emerging and re-emerging RNA viruses induce neuroimmunologic responses that lead to dysfunction of higher order processes including visuospatial recognition, learning and memory, and motor control. Identifying therapeutic targets that return the neuroimmune system to homeostasis is critical for preventing virus-induced neurodegenerative disorders.
许多病毒感染可引起急性和慢性神经系统疾病，导致皮质功能退化。神经嗜性病毒进入中枢神经系统（CNS）后，可能通过感染神经元或其支持细胞直接引起脑损伤，也可能通过间接神经免疫机制改变脑功能，破坏血脑屏障（BBB），消除突触，并产生神经毒性星形胶质细胞和小胶质细胞，从而阻止神经元回路的恢复。非神经侵袭性、神经毒力病毒也可能引发神经胶质细胞的异常反应，包括那些干扰运动和感觉行为、记忆编码和执行功能的反应。越来越多的来自人类和动物研究的证据表明，神经保护抗病毒反应会放大先天免疫分子的水平，从而使正常的神经免疫过程失调，即使在没有神经入侵的情况下也是如此，即使在清除病毒后这种情况仍可能持续存在。在这篇综述中，我们讨论了一些新兴和重新出现的 RNA 病毒如何引起神经免疫反应，导致包括视觉空间识别、学习和记忆以及运动控制在内的高级过程的功能障碍。确定使神经免疫系统恢复到平衡状态的治疗靶点对于预防病毒引起的神经退行性疾病至关重要。
