嗜神经病毒可以通过各种机制通过血脑屏障(BBB)渗入CNS,包括细胞旁,跨细胞,和白细胞透析期间的“特洛伊木马”机制。这些病毒属于几个家族,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,病毒蛋白作用于脑微血管内皮细胞(BMEC)之间的紧密连接(TJs)。例如,HIV-1蛋白,如糖蛋白120,Nef,Vpr,还有Tat,破坏BBB并产生神经毒性作用。重组Tat通过降低TJ蛋白如claudin-1、claudin-5和cloadens-1(ZO-1)的表达来触发BBB中的修正。因此,在包括多发性硬化症(MS)在内的许多神经系统疾病中,已经报道了BBB的破坏。嗜神经病毒还表现出与几种髓鞘蛋白的分子模拟,即,发现抗EBV核抗原1(EBNA1)aa411-426与MBP和EBNA1aa385-420交叉反应的抗体与MS风险单倍型HLA-DRB1*150相关.值得注意的是,髓磷脂蛋白表位(PLP139-151,MOG35-55和MBP87-99)用于生成MS的模型系统,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。如Theiler鼠脑脊髓炎病毒(TMEV)的病毒也通常用于产生EAE。总之,这篇综述提供了有关病毒与BBB渗漏和MS相关的见解,以及可能用于治疗的机制细节。
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 (PLP139-151, MOG35-55, and MBP87-99) 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.