Recently, human T-cell leukemia virus type 1 (HTLV-1) basic leucine zipper factor (HBZ), encoded from a minus strand mRNA was discovered and was suggested to play an important role in adult T cell leukemia (ATL) development. However, there have been no reports on the role of HBZ in patients with HTLV-1 associated inflammatory diseases.

Human T cell leukemia virus type 1 (HTLV-1) basic leucine zipper factor (HBZ), which is encoded by a minus strand mRNA, is thought to play important roles in the development of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). However, a comprehensive analysis of HBZ, including mRNA and protein expression, humoral immunoreactivity against HBZ, and HTLV-1 proviral load (PVL), in HTLV-1-infected individuals with different clinical status has not been reported previously. In this study, using novel monoclonal antibody-based in-house enzyme-linked immunosorbent assay systems, we report the absolute quantification of HBZ protein and its plasma antibody in clinical samples from HTLV-1-infected individuals with different clinical status. The data were compared to both HBZ mRNA levels and PVL. The results showed that plasma anti-HBZ antibody was detectable only in 10.4 % (5/48) of asymptomatic carriers (ACs), 10.8 % (13/120) of HAM/TSP patients, and 16.7 % (7/42) of ATL patients. HBZ protein was detected in three out of five patients with acute ATL, but was not detected in patients with HAM/TSP (0/10) or ACs (0/4). Thus, an antibody response to HBZ was not associated with the PVL or the expression of HBZ (both at the mRNA and protein levels) or the clinical status of the infection. The present results emphasize the extremely low expression and immunogenicity of HBZ in natural HTLV-1 infection. However, there is a possibility that the low but distinct expression of HBZ protein in PBMCs is associated with the survival of HTLV-1-infected cells and the development of ATL.

Human T-cell leukemia virus type 1 (HTLV-1) is a replication-competent human retrovirus associated with two distinct types of diseases: a malignancy of mature CD4⁺ T cells called adult T-cell leukemia-lymphoma (ATL) and a chronic inflammatory central nervous system disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It was the first human retrovirus ever associated with a human cancer. Although most HTLV-1-infected individuals remain asymptomatic for life, a subpopulation develops ATL or HAM/TSP. Although the factors that cause these different manifestations of HTLV-1 infection are not fully understood, accumulating evidence suggests that the complex virus-host interactions, as well as the host immune response against HTLV-1 infection, appear to regulate the development of HTLV-1-associated diseases. This review outlines and discusses the current understanding, ongoing developments, and future perspectives of HTLV-1 research.

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). Although the factors that cause these different manifestations of HTLV-1 infection are not fully understood, accumulating evidence suggests that complex virus-host interactions play an important role in determining the risk of HAM/TSP. This review focuses on the role of the immune response in controlling or limiting viral persistence in HAM/TSP patients, and the reason why some HTLV-1-infected people develop HAM/TSP whereas the majority remains asymptomatic carriers of the virus.

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.

Significance: Human T cell leukemia virus type 1 (HTLV-1) proviral load is associated with the risk of developing HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP) and several small-scale candidate gene approaches have also identified associations of particular HLA alleles with HAM/TSP risk. However, no large-scale genome-wide association (GWA) studies have been performed to date. By a large-scale GWA study and comprehensive genotyping of classical HLA genes, we found that HLA-DRB1 alleles carrying leucine at the antigen presentation groove domain (DRB1-GB-7-Leu) increased the susceptibility to HAM/TSP. Individuals who were homozygous for DRB1-GB-7-Leu had a ninefold increased odds of developing HAM/TSP. This effect of DRB1-GB-7-Leu was independent of proviral load. These findings identify DRB1-GB-7-Leu as a genetic risk marker of HAM/TSP development.