Viral Immunology Section, National Institute of Neurological, Disorders and Stroke, National Institutes of Health, 9000 Rockville Pike, Building 10 Room 5C-103, Bethesda, MD, USA.
Retrovirology. 2019 Nov 29;16(1):35. doi: 10.1186/s12977-019-0499-5.
Human T cell lymphotropic virus 1 (HTLV-1) is a human retrovirus and infects approximately 10-20 million people worldwide. While the majority of infected people are asymptomatic carriers of HTLV-1, only 4% of infected people develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is a chronic, progressive, neurological disease which usually progresses slowly without remission, and is characterized by perivascular inflammatory infiltrates in chronic inflammatory lesions of the central nervous system (CNS), primarily affecting the spinal cord. A high HTLV-1 proviral load, high levels of antibodies against HTLV-1 antigens, and elevated concentration of proteins are detected in cerebrospinal fluid (CSF) of HAM/TSP patients. These chronically activated immune responses against HTLV-1 and infiltration of inflammatory cells including HTLV-1 infected cells into the CNS contribute to clinical disability and underlie the pathogenesis of HAM/TSP. Since the disease development of HAM/TSP mainly occurs in adults, with a mean age at onset of 40-50 years, it is important for HTLV-1-infected carriers and HAM/TSP patients to be monitored throughout the disease process. Recent advances in technologies and findings provide new insights to virological and immunological aspects in both the CNS as well as in peripheral blood. In this review, we focus on understanding the inflammatory milieu in the CNS and discuss the immunopathogenic process in HTLV-1-associated neurologic diseases.
人类 T 细胞嗜淋巴细胞病毒 1(HTLV-1)是一种人类逆转录病毒,全球约有 1000 万至 2000 万人感染。虽然大多数感染者是无症状的 HTLV-1 携带者,但只有 4%的感染者会发展为 HTLV-1 相关性脊髓病/热带痉挛性截瘫(HAM/TSP)。HAM/TSP 是一种慢性、进行性、神经系统疾病,通常无缓解地缓慢进展,其特征是中枢神经系统(CNS)慢性炎症病变中有血管周围炎症浸润,主要影响脊髓。HAM/TSP 患者的脑脊液(CSF)中可检测到高 HTLV-1 前病毒载量、高水平的抗 HTLV-1 抗原抗体和升高的蛋白浓度。这些针对 HTLV-1 的慢性激活免疫反应以及包括感染 HTLV-1 的细胞在内的炎症细胞浸润到中枢神经系统,导致临床残疾,并构成 HAM/TSP 的发病机制。由于 HAM/TSP 的疾病发展主要发生在成年人中,发病平均年龄为 40-50 岁,因此对 HTLV-1 感染的携带者和 HAM/TSP 患者进行全程监测非常重要。技术和研究结果的最新进展为 CNS 及外周血中的病毒学和免疫学方面提供了新的见解。在这篇综述中,我们重点关注对 CNS 中炎症环境的理解,并讨论 HTLV-1 相关性神经疾病中的免疫发病机制。