To investigate the role of viral expression in individuals infected with human T-cell lymphotropic virus type 1 (HTLV-1), a real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) of HTLV-1 tax messenger RNA (mRNA) using ABI Prism 7700 Sequence Detection System was developed. Using this system, the HTLV-1 tax mRNA load was compared with HTLV-1 proviral DNA load, HTLV-1 Tax protein expression, HTLV-1 Tax-specific CD8(+) T-cell frequency, and disease severity of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). This approach was a sensitive and specific technique for the precise quantification of HTLV-1 tax mRNA. The total amount of HTLV-1 tax mRNA and mRNA expression level in HTLV-1-infected cells (mRNA/DNA ratio) were higher in HAM/TSP patients than in asymptomatic HTLV-1 carriers. The HTLV-1 tax mRNA load correlated with the HTLV-1 proviral DNA load ex vivo, the Tax protein expression in vitro, and the Tax-specific CD8(+) T-cell frequency ex vivo. The HTLV-1 tax mRNA load also correlated with disease severity in HAM/TSP patients. These data suggest that increased HTLV-1 expression plays an important role in the pathogenesis of HAM/TSP, and the HTLV-1 tax mRNA level could be a useful predictor of disease progression in patients with HAM/TSP.

Human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive disease of the CNS that causes weakness or paralysis of the legs, lower back pain and urinary symptoms. HAM/TSP was first described in Jamaica in the nineteenth century, but the aetiology of the condition, infection with the retrovirus HTLV-1, was only identified in the 1980s. HAM/TSP causes chronic disability and, accordingly, imposes a substantial health burden in areas where HTLV-1 infection is endemic. Since the discovery of the cause of HAM/TSP, considerable advances have been made in the understanding of the virology, immunology, cell biology and pathology of HTLV-1 infection and its associated diseases. However, progress has been limited by the lack of accurate animal models of the disease. Moreover, the treatment of HAM/TSP remains highly unsatisfactory: antiretroviral drugs have little impact on the infection and, although potential disease-modifying therapies are widely used, their value is unproved. At present, clinical management is focused on symptomatic treatment and counselling. Here, we summarize current knowledge on the epidemiology, pathogenesis and treatment of HAM/TSP and identify areas in which further research is needed. For an illustrated summary of this Primer, visit: http://go.nature.com/tjZCFM.

To date, high human T-cell lymphotropic virus type I proviral load in patients with human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis has been reported and is thought to be related to the pathogenesis of human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis. However, the proviral load in cerebrospinal fluid has not been well investigated. We measured human T-cell lymphotropic virus type I proviral load in cerebrospinal fluid cells from human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis patients using real-time quantitative polymerase chain reaction (TaqMan). Human T-cell lymphotropic virus type I proviral load in cerebrospinal fluid cells were significantly higher than that of the matched peripheral blood mononuclear cells, and a high ratio of human T-cell lymphotropic virus type I proviral load in cerebrospinal fluid cells to peripheral blood mononuclear cells were observed in patients with short duration of illness. Human T-cell lymphotropic virus type I Tax-specific CD8+ T cells, as detected by peptide-loaded HLA tetramers, accumulated in cerebrospinal fluid compared with that in peripheral blood mononuclear cells, while the frequency of cytomegalovirus-specific CD8+ T cells in cerebrospinal fluid was reduced. These observations suggest that accumulation of both human T-cell lymphotropic virus type I-infected cells and preferential expansion of human T-cell lymphotropic virus type I-specific CD8+ cells in cerebrospinal fluid may play a role in the pathogenesis of human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis.