Neurotropic viruses can infiltrate the CNS by crossing the blood–brain barrier (BBB) through various mechanisms including paracellular, transcellular, and “Trojan horse” mechanisms during leukocyte diapedesis. These viruses belong to several families, including retroviruses; human immunodeficiency virus type 1 (HIV-1), flaviviruses; Japanese encephalitis (JEV); and herpesviruses; herpes simplex virus type 1 (HSV-1), Epstein-Barr virus (EBV), and mouse adenovirus 1 (MAV-1). For entering the brain, viral proteins act upon the tight junctions (TJs) between the brain microvascular endothelial cells (BMECs). For instance, HIV-1 proteins, such as glycoprotein 120, Nef, Vpr, and Tat, disrupt the BBB and generate a neurotoxic effect. Recombinant-Tat triggers amendments in the BBB by decreasing expression of the TJ proteins such as claudin-1, claudin-5, and zona occludens-1 (ZO-1). Thus, the breaching of BBB has been reported in myriad of neurological diseases including multiple sclerosis (MS). Neurotropic viruses also exhibit molecular mimicry with several myelin sheath proteins, i.e., antibodies against EBV nuclear antigen 1 (EBNA1) aa411–426 cross-react with MBP and EBNA1 aa385–420 was found to be associated with MS risk haplotype HLA-DRB1*150. Notably, myelin protein epitopes (PLP_139-151, MOG_35-55, and MBP_87-99) are being used to generate model systems for MS such as experimental autoimmune encephalomyelitis (EAE) to understand the disease mechanism and therapeutics. Viruses like Theiler’s murine encephalomyelitis virus (TMEV) are also commonly used to generate EAE. Altogether, this review provide insights into the viruses’ association with BBB leakiness and MS along with possible mechanistic details which could potentially use for therapeutics.

嗜神经病毒可以通过多种机制穿过血脑屏障（BBB）渗透中枢神经系统，包括细胞旁、跨细胞和白细胞渗出过程中的“特洛伊木马”机制。这些病毒属于多个家族，包括逆转录病毒；人类免疫缺陷病毒 1 型 (HIV-1)、黄病毒；日本脑炎（JEV）；和疱疹病毒；单纯疱疹病毒 1 型 (HSV-1)、EB 病毒 (EBV) 和小鼠腺病毒 1 (MAV-1)。为了进入大脑，病毒蛋白作用于大脑微血管内皮细胞（BMEC）之间的紧密连接（TJ）。例如，HIV-1 蛋白，如糖蛋白 120、Nef、Vpr 和 Tat，会破坏 BBB 并产生神经毒性作用。 Recombinant-Tat 通过降低 TJ 蛋白（例如claudin-1、claudin-5 和 zona occlusionns-1 (ZO-1)）的表达来触发 BBB 的修正。因此，BBB 的破坏已在包括多发性硬化症 (MS) 在内的多种神经系统疾病中得到报道。嗜神经病毒还表现出与多种髓鞘蛋白的分子拟态性，即针对 EBV 核抗原 1 (EBNA1) aa411-426 的抗体与 MBP 发生交叉反应，并且发现 EBNA1 aa385-420 与 MS 风险单倍型 HLA-DRB1*150 相关。值得注意的是，髓磷脂蛋白表位（PLP _139-151 、MOG _35-55和 MBP _87-99 ）被用来生成 MS 模型系统，例如实验性自身免疫性脑脊髓炎 (EAE)，以了解疾病机制和治疗方法。泰勒氏鼠脑脊髓炎病毒 (TMEV) 等病毒也常用于产生 EAE。 总而言之，这篇综述提供了对病毒与血脑屏障渗漏和多发性硬化症之间关系的深入了解，以及可能用于治疗的可能机制细节。