Abstract
HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a neuropathological disorder in 1–3% of individuals infected with Human T-lymphotropic virus 1 (HTLV-1). This condition is characterized by progressive spastic lower limb weakness and paralysis, lower back pain, bladder incontinence, and mild sensory disturbances resembling spinal forms of multiple sclerosis. This disease also causes chronic disability and is therefore associated with high health burden in areas where HTLV-1 infection is endemic. Despite various efforts in understanding the virus and discovery of novel diagnostic markers, and cellular and viral interactions, HAM/TSP management is still unsatisfactory and mainly focused on symptomatic alleviation, and it hasn’t been explained why only a minority of the virus carriers develop HAM/TSP. This comprehensive review focuses on host and viral factors in association with immunopathology of the disease in hope of providing new insights for drug therapies or other forms of intervention.
Highlights
Human T-lymphotropic virus type 1 (HTLV-1), discovered in 1980, is a retrovirus from the Orthoretrovirinae subfamily of Deltaretrovirus genus
Evidence suggests that aberrant function of these cells in Human T-lymphotropic virus 1 (HTLV-1)-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) may be the result of various factors including: high antigenic stimulation, Tax dysregulation of cytokine loops (IL-2/IL2R and IL-15/IL-15R), and selective expression of surface receptors (CD244) which results in reduction of T-cell avidity, spontaneous degranulation, excessive cytokine expression (IFN-γ, Tumor necrosis factor (TNF), and IL-2) and subsequent damage to the host tissues (Kubota et al, 1998; Enose-Akahata et al, 2008, 2017; Sabouri et al, 2008; Kattan et al, 2009; YasumaMitobe and Matsuoka, 2018; Nozuma and Jacobson, 2019)
Humoral immune responses against Gag and Env are significantly increased in blood of HAM/TSP vs. other HTLV-1 infected individuals; whereas anti-Tax and anti-HTLV-1 Basic Zipper Factor (HBZ) Ab levels are similar in HTLV-1 infected subjects (Enose-Akahata et al, 2012a; Shiohama et al, 2016)
Summary
Human T-lymphotropic virus type 1 (HTLV-1), discovered in 1980, is a retrovirus from the Orthoretrovirinae subfamily of Deltaretrovirus genus. Tax as a viral protein affects several cellular pathways, leading to changes in host gene expression, T-cell differentiation, and modification of immune response.
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