Brand A, Griffiths D J, Herve C, Mallon E, Venables P J
Chelsea and Westminster Hospital, London, UK.
J Autoimmun. 1999 Aug;13(1):149-54. doi: 10.1006/jaut.1999.0307.
It has long been suggested that retroviral infection may play a role in the pathogenesis of autoimmune rheumatic disease. Particles resembling retroviruses have been reported in tissue from patients with Sjögren's syndrome, lupus and rheumatoid arthritis, and molecular mimicry between retroviral antigens and host proteins has been proposed as a mechanism of induction of autoimmunity. Since 1980, four distinct human infectious retroviruses have been discovered, HTLV-I, HTLV-II, HIV-1 and HIV-2. We recently cloned part of a new human retrovirus genome, designated human retrovirus-5 (HRV-5) and demonstrated that this is not endogenous and is therefore a novel infectious retrovirus. Because symptoms resembling arthritis, polymyositis and Sjögren's syndrome occur in individuals infected with HTLV-I and HIV-1, we investigated the possibility that HRV-5 was associated with idiopathic rheumatic disease. Using nested PCR, HRV-5 we demonstrated that proviral DNA was present in approximately 50% of synovial samples of arthritic joints and was also found in over 10% of blood samples of patients with rheumatoid arthritis and systemic lupus erythematosus. HRV-5 proviral DNA was not detectable in affected tissues of autoimmune diseases and was found in only one of over 200 tissues taken at autopsy from non-rheumatoid patients. Sequence analysis of the amplified viral segment showed genetic variation between samples with maintenance of the open reading frame typical of a replicating infectious retrovirus. Thus HRV-5 appears to be a human retrovirus found with a very low genome copy number in most tissues, but which is increased to detectable levels in inflamed joints and blood from patients with rheumatic disease. Whether HRV-5 is aetiologically important in these diseases remains to be determined.
长期以来,人们一直认为逆转录病毒感染可能在自身免疫性风湿性疾病的发病机制中起作用。在干燥综合征、狼疮和类风湿性关节炎患者的组织中已报告有类似逆转录病毒的颗粒,并且有人提出逆转录病毒抗原与宿主蛋白之间的分子模拟是诱导自身免疫的一种机制。自1980年以来,已发现四种不同的人类感染性逆转录病毒,即HTLV-I、HTLV-II、HIV-1和HIV-2。我们最近克隆了一种新的人类逆转录病毒基因组的一部分,命名为人类逆转录病毒-5(HRV-5),并证明它不是内源性的,因此是一种新型感染性逆转录病毒。由于感染HTLV-I和HIV-1的个体出现类似关节炎、多发性肌炎和干燥综合征的症状,我们研究了HRV-5与特发性风湿性疾病相关的可能性。通过巢式PCR,我们证明在大约50%的关节炎关节滑膜样本中存在前病毒DNA,并且在类风湿性关节炎和系统性红斑狼疮患者的超过10%的血液样本中也发现了该病毒。在自身免疫性疾病的受累组织中未检测到HRV-5前病毒DNA,并且在从非类风湿患者尸检获取的200多个组织中仅在一个组织中发现了该病毒。对扩增的病毒片段进行序列分析显示样本之间存在基因变异,同时保留了复制性感染性逆转录病毒典型的开放阅读框。因此,HRV-5似乎是一种在大多数组织中以非常低的基因组拷贝数存在的人类逆转录病毒,但在风湿性疾病患者的炎症关节和血液中其拷贝数增加到可检测水平。HRV-5在这些疾病中是否具有病因学重要性仍有待确定。