Abstract
Human T-lymphotropic virus type 1 (HTLV-1) is the etiologic agent of both adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is clinically characterized by chronic progressive spastic paraparesis, urinary incontinence, and mild sensory disturbance. Given its well-characterized clinical presentation and pathophysiology, which is similar to the progressive forms of multiple sclerosis (MS), HAM/TSP is an ideal system to better understand other neuroimmunological disorders such as MS. Since the discovery of HAM/TSP, large numbers of clinical, virological, molecular, and immunological studies have been published. The host-virus interaction and host immune response play an important role for the development with HAM/TSP. HTLV-1-infected circulating T-cells invade the central nervous system (CNS) and cause an immunopathogenic response against virus and possibly components of the CNS. Neural damage and subsequent degeneration can cause severe disability in patients with HAM/TSP. Little progress has been made in the discovery of objective biomarkers for grading stages and predicting progression of disease and the development of molecular targeted therapy based on the underlying pathological mechanisms. We review the recent understanding of immunopathological mechanism of HAM/TSP and discuss the unmet need for research on this disease.
Highlights
Human T-lymphotropic virus type 1 (HTLV-1) is the first human retrovirus discovered and infects 10–20 million people worldwide (Poiesz et al, 1980; de The and Bomford, 1993)
These results indicate that oligoclonal proliferation of HTLV-1-infected cells does not account for the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and clonal expansion of infected cells might be controlled by host immune response to Tax or by other viral factor such as HTLV-1 basic leucine zipper factor (HBZ) in HAM/TSP patients
Higher levels of matrix metalloproteinase (MMP)-2 and MMP-9 were detected in the cerebrospinal fluid (CSF) and in infiltrating perivascular mononuclear cells in active lesions in the central nervous system (CNS), indicating that MMP-2 and MMP-9 may play a key role in the blood-brain barrier (BBB) breakdown in HAM/TSP patients (Umehara et al, 1998)
Summary
Viral Immunology Section, Division of Neuroimmunology and Neurovirology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States. Human T-lymphotropic virus type 1 (HTLV-1) is the etiologic agent of both adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is clinically characterized by chronic progressive spastic paraparesis, urinary incontinence, and mild sensory disturbance. Given its well-characterized clinical presentation and pathophysiology, which is similar to the progressive forms of multiple sclerosis (MS), HAM/TSP is an ideal system to better understand other neuroimmunological disorders such as MS. Since the discovery of HAM/TSP, large numbers of clinical, virological, molecular, and immunological studies have been published. The host-virus interaction and host immune response play an important role for the development with HAM/TSP. We review the recent understanding of immunopathological mechanism of HAM/TSP and discuss the unmet need for research on this disease
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