Fierz Walter
labormedizinisches zentrum Dr Risch, Vaduz, Liechtenstein.
Front Immunol. 2017 Oct 17;8:1314. doi: 10.3389/fimmu.2017.01314. eCollection 2017.
Viruses are able to interfere with the immune system by docking to receptors on host cells that are important for proper functioning of the immune system. A well-known example is the human immunodeficiency virus that uses CD4 cell surface molecules to enter host lymphocytes and thereby deleteriously destroying the helper cell population of the immune system. A more complicated mechanism is seen in multiple sclerosis (MS) where human herpes virus-6A (HHV-6A) infects astrocytes by docking to the CD46 surface receptor. Such HHV-6A infection in the brain of MS patients has recently been postulated to enable Epstein-Barr virus (EBV) to transform latently infected B-lymphocytes in brain lesions leading to the well-known phenomenon of oligoclonal immunoglobulin production that is widely used in the diagnosis of MS. The cellular immune response to HHV-6A and EBV is one part of the pathogenic mechanisms in MS. A more subtle pathogenic mechanism can be seen in the downregulation of CD46 on astrocytes by the infecting HHV-6A. Since CD46 is central in regulating the complement system, a lack of CD46 can lead to hyperactivation of the complement system. In fact, activation of the complement system in brain lesions is a well-known pathogenic mechanism in MS. In this review, it is postulated that a similar mechanism is central in the development of age-related macular degeneration (AMD). One of the earliest changes in the retina of AMD patients is the loss of CD46 expression in the retinal pigment epithelial (RPE) cells in the course of geographic atrophy. Furthermore, CD46 deficient mice spontaneously develop dry-type AMD-like changes in their retina. It is also well known that certain genetic polymorphisms in the complement-inhibiting pathways correlate with higher risks of AMD development. The tenet is that HHV-6A infection of the retina leads to downregulation of CD46 and consequently to hyperactivation of the complement system in the eyes of susceptible individuals.
病毒能够通过与宿主细胞上对免疫系统正常功能至关重要的受体结合来干扰免疫系统。一个众所周知的例子是人类免疫缺陷病毒，它利用CD4细胞表面分子进入宿主淋巴细胞，从而有害地破坏免疫系统的辅助细胞群体。在多发性硬化症（MS）中可以看到一种更复杂的机制，其中人类疱疹病毒6A（HHV-6A）通过与CD46表面受体结合感染星形胶质细胞。最近有人推测，MS患者大脑中的这种HHV-6A感染能使爱泼斯坦-巴尔病毒（EBV）转化脑损伤中潜伏感染的B淋巴细胞，导致广泛用于MS诊断的寡克隆免疫球蛋白产生这一众所周知的现象。对HHV-6A和EBV的细胞免疫反应是MS致病机制的一部分。在感染的HHV-6A导致星形胶质细胞上CD46下调的过程中，可以看到一种更微妙的致病机制。由于CD46在调节补体系统中起核心作用，CD46的缺乏会导致补体系统过度激活。事实上，脑损伤中补体系统的激活是MS中一种众所周知的致病机制。在本综述中，有人推测类似的机制在年龄相关性黄斑变性（AMD）的发展中起核心作用。AMD患者视网膜最早的变化之一是在地图状萎缩过程中视网膜色素上皮（RPE）细胞中CD46表达的丧失。此外，CD46缺陷小鼠的视网膜会自发出现干性AMD样变化。众所周知，补体抑制途径中的某些基因多态性与AMD发生的较高风险相关。其原理是视网膜的HHV-6A感染导致CD46下调，从而导致易感个体眼睛中的补体系统过度激活。
