Department of Viroscience, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands.
Viruses. 2022 Sep 21;14(10):2096. doi: 10.3390/v14102096.
Many arboviruses, including viruses of the genera, are known to cause severe neurological disease in humans, often with long-lasting, debilitating sequalae in surviving patients. These emerging pathogens impact millions of people worldwide, yet still relatively little is known about the exact mechanisms by which they gain access to the human central nervous system. This review focusses on potential haematogenous and transneural routes of neuroinvasion employed by flaviviruses and identifies numerous gaps in knowledge, especially regarding lesser-studied interfaces of possible invasion such as the blood-cerebrospinal fluid barrier, and novel routes such as the gut-brain axis. The complex balance of pro-inflammatory and antiviral immune responses to viral neuroinvasion and pathology is also discussed, especially in the context of the hypothesised Trojan horse mechanism of neuroinvasion. A greater understanding of the routes and mechanisms of arboviral neuroinvasion, and how they differ between viruses, will aid in predictive assessments of the neuroinvasive potential of new and emerging arboviruses, and may provide opportunity for attenuation, development of novel intervention strategies and rational vaccine design for highly neurovirulent arboviruses.
许多虫媒病毒，包括黄病毒属和西尼罗病毒属的病毒，已知会导致人类严重的神经系统疾病，存活的患者通常会留下持久的、使人虚弱的后遗症。这些新出现的病原体影响着全世界数百万人，但人们对它们进入人类中枢神经系统的确切机制仍然知之甚少。本综述重点关注黄病毒可能采用的血源性和经神经传播的神经入侵途径，并确定了许多知识空白，特别是对于潜在入侵的较少研究的界面，如血脑屏障，以及新的途径，如肠道-大脑轴。还讨论了针对病毒神经入侵和病理学的促炎和抗病毒免疫反应的复杂平衡，特别是在神经入侵的特洛伊木马机制假设的背景下。对虫媒病毒神经入侵的途径和机制，以及它们在不同病毒之间的差异有更深入的了解，将有助于预测新出现的虫媒病毒的神经入侵潜力，并可能为高度神经毒力的虫媒病毒提供减毒、开发新的干预策略和合理的疫苗设计的机会。
