Center for Alternatives to Animal Testing, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
Division of Neuroimmunology, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Front Cell Infect Microbiol. 2019 Jul 9;9:223. doi: 10.3389/fcimb.2019.00223. eCollection 2019.
Mosquito-borne flaviviruses can cause disease in the nervous system, resulting in a significant burden of morbidity and mortality. Disease models are necessary to understand neuropathogenesis and identify potential therapeutics and vaccines. Non-human primates have been used extensively but present major challenges. Advances have also been made toward the development of humanized mouse models, but these models still do not fully represent human pathophysiology. Recent developments in stem cell technology and cell culture techniques have allowed the development of more physiologically relevant human cell-based models. modeling has also allowed researchers to identify and predict transmission patterns and discover potential vaccine and therapeutic candidates. This review summarizes the research on and models used to study three mosquito-borne flaviviruses that cause neurological disease in humans: West Nile, Dengue, and Zika. We also propose a roadmap for 21st century research on mosquito-borne flavivirus neuropathogenesis, prevention, and treatment.
蚊媒黄病毒可引起神经系统疾病，导致发病率和死亡率的显著负担。需要疾病模型来了解神经发病机制并确定潜在的治疗方法和疫苗。非人类灵长类动物已被广泛使用，但存在重大挑战。在开发人源化小鼠模型方面也取得了进展，但这些模型仍不能完全代表人类病理生理学。干细胞技术和细胞培养技术的最新进展使得更具生理相关性的基于人类细胞的模型得以开发。模型还使研究人员能够识别和预测传播模式，并发现潜在的疫苗和治疗候选物。本文综述了用于研究三种引起人类神经疾病的蚊媒黄病毒的 和 模型：西尼罗河病毒、登革热病毒和寨卡病毒。我们还提出了蚊媒黄病毒神经发病机制、预防和治疗的 21 世纪研究路线图。
