HTLV-1-associated myelopathy/tropical spastic paraparesis

Abstract

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.

HTLV-1 bZIP Factor Enhances T-Cell Proliferation by Impeding the Suppressive Signaling of Co-inhibitory Receptors

“…HTLV-1 causes adult T-cell leukemia-lymphoma (ATL) and inflammatory diseases [1–4]. This virus induces clonal proliferation of infected cells to enhance its transmission, since HTLV-1 is transmitted primarily by cell-to-cell contact [5–7].…”

Reducing the global burden of HTLV-1 infection: An agenda for research and action

“…This article presents the consensus views of taskforce members regarding unsolved or controversial issues that hamper further understanding of HTLV-1 and the development of new approaches for diagnosis, prevention and therapy. For additional information on the molecular mechanisms of pathogenesis, immunological aspects, epidemiology and currently available therapies for HTLV-1 infection, readers are referred to a number of excellent review articles (Bangham et al, 2015;Matsuoka and Jeang, 2007;Pique and Jones, 2012;Murphy, 2016;Gessain and Cassar, 2012;Kato and Akashi, 2015).…”

How does human T‐lymphotropic virus type 1 cause central nervous system disease? The importance of cross‐talk between infected T cells and astrocytes

“…HTLV‐1 is a human retrovirus endemic to Japan, the Caribbean, South America and Africa . There are more than 1 million people infected in Japan alone, and approximately 20 million people worldwide .…”

“…The life expectancy of ATL patients is only about 1 year. In addition, approximately 0.3–3.8% of HTLV‐1 carriers develop the debilitating inflammation in the spinal cord that characterizes HAM/TSP . As the spinal cord is mainly affected in HAM/TSP, the major symptoms are lower limb paralysis, pain, dysuria and constipation.…”

“…As the spinal cord is mainly affected in HAM/TSP, the major symptoms are lower limb paralysis, pain, dysuria and constipation. As symptoms progress, patients might become wheelchair‐bound or even bedridden . Unfortunately, there is no cure for this disease.…”