Introduction

The exogenous human retrovirus human T-lymphotropic virus type 1 (HTLV-1) results in a highly dynamic persistent infection that has a significant clinical impact in endemic areas. HTLV-1 usually causes an asymptomatic infection, but in a small proportion of individuals disease may develop: adult T-cell leukemia or a range of inflammatory diseases. Of these inflammatory diseases HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is the most studied. HAM/TSP is a chronic inflammatory disease of the central nervous system. It is rarely fatal, but can be severely debilitating. HTLV-1 is not a classical neurotropic virus and does not directly infect the cells of the central nervous system (CNS). Instead, HTLV-1 is found primarily within infiltrating, infected CD4+ T lymphocytes. CD4+ T-cell infiltration into the CNS is currently believed to be the pivotal event for the pathogenesis of HAM/TSP. Here we describe the immune control of HTLV-1 infection in the periphery and discuss its relationship with inflammation in the CNS. We explore the current hypothesis of HAM/TSP pathogenesis, identify crucial factors, and suggest a new hypothesis focused on why the majority of HTLV-1-infected individuals do not develop neuroinflammatory disease.

HTLV-1

HTLV-1 was the first exogenous replication competent human retrovirus to be identified over 20 years ago by Poiesz et al. [1]. HTLV-1 virions were isolated from a cell line established from a cutaneous T-cell lymphoma. HTLV-1 has since been associated with two different types of disease: lymphoma/leukemia and chronic inflammatory diseases [2, 3, 4, 5].