Human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis: Clinical presentation and pathophysiology

Human T-cell lymphotropic virus type 1(HTLV-1)-associated myelopathy/tropical spastic paraparesis(HAM/TSP) is a slowly progressive neurodegenerative disorder in which lesions of the central nervous system cause progressive weakness, stiffness, and a lower limb spastic paraparesis. In some cases, polymyositis, inclusion bodymyositis, or amyotrophic lateral sclerosis-like syndromes are associated with HTLV-1. TSP was first described in Jamaica in 1888 and known as Jamaican peripheral neuritis before TSP was related to HTLV-1 virus, the first retrovirus being identified, and the disease is since named HAM/TSP. There is no established treatment program for HAM/TSP. Prevention is difficult in lowincome patients(i.e., HTLV-1 infected breast feeding mothers in rural areas, sex workers). Thus, there is a need for new therapeutic avenues. Therapeutic approaches must be based on a better understanding, not only of clinical and clinicopathological data, but also of the pathophysiology of the affection. Consequently, a better understanding of existing or newly developed animal models of HAM/TSP is a prerequisite step in the development of new treatments.

Co-expression of HBZ,TAX and FOXp3 and HTLV-1-associated myelopathy/tropical spastic paraparesis development in HTLV-1-infected individuals:A systematic review

Human T-cell lymphotropic virus type 1(HTLV-1)is associated with the development of HTLV-1-associated myelopathy/tropical spastic paraparesis(HAM/TSP).It has been reported that the HTLV-1 proteins(specifically TAX and HBZ)can modulate FOXp3,resulting in an immune imbalance that can favor the progression of HAM/TSP.This review aims to summarize the literature in order to clarify the relationship between the expression of HTLV-1 m RNAs and/or viral proteins(TAX and HBZ)with the expression of mRNA and/or protein FOXp3 and their correlation with HAM/TSP development.This systematic review was conducted according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis.The search strategy was performed on the Medical Literature Analysis and Retrieval System Online and Latin American and Caribbean Literature in Health Sciences Platform using subject descriptors.After screening,six articles were included in this review.The studies suggested that TAX and HBZ have a directly proportional correlation with FOXp3 in individuals with HAM/TSP,which also presented an increased expression of FOXp3 compared to asymptomatic controls and/or healthy donors.This systematic review indicates that TAX and HBZ can interact with FOXp3 and that interaction may influence HAM/TSP development.

Role of post-translational modifications of HTLV-1 Tax in NF-κB activation

Human T-cell leukemia virus type 1(HTLV-1),the first human retrovirus discovered,is the etiological agent of adult-T-cell leukemia/lymphoma.The HTLV-1 encoded Tax protein is a potent oncoprotein that deregulates gene expression by constitutively activating nuclear factor-κB(NF-κB).Tax activation of NF-κB is critical for the immortalization and survival of HTLV-1-infected T cells.In this review,we summarize the present knowledge on mechanisms underlying Tax-mediated NF-κB activation,with an emphasis on post-translational modifications of Tax.

人嗜T淋巴细胞Ⅰ型病毒(HTLV-Ⅰ)与神经系统疾病关系的初步研究

1980年,美国的Poiesy和日本的Miyoshi等先后发现人类第一个C型逆转录病毒,后国际上统一命名为人嗜T淋巴细胞Ⅰ型病毒(HTLV-1)。这类病毒以人T_4细胞亚群为靶细胞,并与成人T细胞白血病有病原学关系。1985年,Gessain等报告在热痉挛性瘫痪病人(Tropical Spastic Paraparesis,TSP)血清和脑脊液中查出HTLV-Ⅰ抗体,1986年又在Colombia、Jamaica、Trinidad、Tobago和Ivory Coast等一些国家和地区,也发现某些慢性脊髓神经病变患者(症状相似于TSP病人)的血清和脑脊液中有HTLV-Ⅰ抗体存在。

A novel mouse model of adult T-cell leukemia cell invasion into the spinal cord

Adult T-cell leukemia( ATL) is a mature T-cell malignancy caused by human T-cell leukemia virus type I infection, and 10%-25% of patients show central nervous system( CNS) involvement. CNS involvement significantly reduces survival and there are no effective treatments for CNS involvement. Therefore, an appropriate animal model is required to evaluate the inhibitory effects of novel drugs on the progression of ATL with CNS involvement. Here, we established a mouse model of ATL with CNS involvement using NOD.Cg-Prkdc~ (scid) Il2 rg ^(tm1Wjl)/SzJ mice inoculated with ATL cells intramuscularly in the postauricular region, and these mice showed paraparesis. Of the 10 mice inoculated with ATL cells intramuscularly(I.M.) at 5 weeks of age, 8(80%) showed paraparesis, whereas none of the 10 mice inoculated with ATL cells subcutaneously(S.C.) showed paraparesis. In the I.M. group, PCR detected HTLV-1-specific genes in the thoracic and lumbar vertebrae; however, in the S.C. group, the vertebrae were negative for HTLV-1 genes. Histological analysis revealed a particularly high incidence of tumors, characterized by accumulation of the injected cells, in the thoracic vertebrae of mice in the I.M. group. Tumor cell infiltration was relatively high in the bone marrow. Spinal cord compression caused by invasion of the tumor mass outside the pia mater was observed in the thoracic vertebrae of the spinal cord. In conclusion, we have reported a mouse model of tumor growth with paraparesis that may be used to assess novel therapeutic agents for ATL with CNS involvement.