Donati Donatella
Neurologia e Neurofisiologia Clinica, Azienda Ospedaliera Universitaria Senese I 53100 Siena, Italy.
Drug Discov Today Dis Models. 2020 Fall;32:27-33. doi: 10.1016/j.ddmod.2020.02.003. Epub 2020 Mar 1.
The etiology and pathogenesis of MS is likely to involve multiple factors interacting with each other, and the role of infectious and viral agents is still under debate, however a consistent amount of studies suggests that some viruses are associated with the disease. The strongest documentation has come from the detection of viral nucleic acid or antigen or of an anti-viral antibody response in MS patients. A further step for the study of the mechanism viruses might be involved in can be made using and models. While models, based on glial and neural cell lines from various sources are widely used, animal models present challenges. Indeed neurotropic animal viruses are currently used to study demyelination in well-established models, but animal models of demyelination by human virus infection have only recently been developed, using animal gammaherpesviruses closely related to Epstein Barr virus (EBV), or using marmosets expressing the specific viral receptor for Human Herpesvirus 6 (HHV-6). The present review will illustrate the main potential mechanisms of MS pathogenesis possibly associated with viral infections and viruses currently used to study demyelination in animal models. Then the viruses most strongly linked with MS will be discussed, in the perspective that more than one virus might have a role, with varying degrees of interaction, contributing to MS heterogeneity.
多发性硬化症(MS)的病因和发病机制可能涉及多种相互作用的因素,感染因子和病毒的作用仍存在争议,然而大量研究表明某些病毒与该疾病有关。最有力的证据来自于在MS患者中检测到病毒核酸、抗原或抗病毒抗体反应。利用[具体模型名称1]和[具体模型名称2]模型可以进一步研究病毒可能涉及的机制。虽然基于各种来源的神经胶质细胞系和神经细胞系的[具体模型名称1]模型被广泛使用,但[具体模型名称2]动物模型存在挑战。确实,嗜神经动物病毒目前被用于在成熟的模型中研究脱髓鞘,但人类病毒感染导致脱髓鞘的动物模型直到最近才得以开发,使用与爱泼斯坦-巴尔病毒(EBV)密切相关的动物γ疱疹病毒,或使用表达人类疱疹病毒6型(HHV-6)特异性病毒受体的狨猴。本综述将阐述MS发病机制中可能与病毒感染相关的主要潜在机制,以及目前用于在动物模型中研究脱髓鞘的病毒。然后将讨论与MS联系最为紧密的病毒,考虑到可能不止一种病毒在不同程度的相互作用下对MS的异质性起作用。