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. 2012:2012:259045.
doi: 10.1155/2012/259045. Epub 2012 Feb 6.

Immunopathogenesis of human T-cell leukemia virus type-1-associated myelopathy/tropical spastic paraparesis: recent perspectives

Affiliations

Immunopathogenesis of human T-cell leukemia virus type-1-associated myelopathy/tropical spastic paraparesis: recent perspectives

Mineki Saito et al. Leuk Res Treatment. 2012.

Abstract

Human T-cell leukemia virus type-1 (HTLV-1) is a replication-competent human retrovirus associated with two distinct types of disease only in a minority of infected individuals: the malignancy known as adult T-cell leukemia (ATL) and a chronic inflammatory central nervous system disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is a chronic progressive myelopathy characterized by spastic paraparesis, sphincter dysfunction, and mild sensory disturbance in the lower extremities. Although the factors that cause these different manifestations of HTLV-1 infection are not fully understood, accumulating evidence from host population genetics, viral genetics, DNA expression microarrays, and assays of lymphocyte function suggests that complex virus-host interactions and the host immune response play an important role in the pathogenesis of HAM/TSP. Especially, the efficiency of an individual's cytotoxic T-cell (CTL) response to HTLV-1 limits the HTLV-1 proviral load and the risk of HAM/TSP. This paper focuses on the recent advances in HAM/TSP research with the aim to identify the precise mechanisms of disease, in order to develop effective treatment and prevention.

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Figures

Figure 1
Figure 1
Hypothesis for the pathogenesis of human T-cell leukemia virus type-1 (HTLV-1) -associated myelopathy/tropical spastic paraparesis (HAM/TSP). Accumulating evidence suggests that the virus-host immunologic interactions play a pivotal role in HAM/TSP pathogenesis. Genetically determined less efficient CTL response against HTLV-1 may cause higher proviral load and antigen expression in infected individuals, which lead to activation and expansion of antigen-specific T-cell responses, subsequent induction of large amounts of proinflammatory cytokines and chemokines, and progression of HAM/TSP development. It is also possible that the immunoglobulin G specific to HTLV-1-Tax, which cross-react with heterogeneous nuclear ribonuclear protein-A1 (hnRNP-A1), is associated with subsequent inflammation following initial tissue damage.

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