HTLV-1-associated diseases.

Abstract

HTLV-1-infection is associated with a variety of human diseases including adult T-cell leukemia (ATL) and non-neoplastic inflammatory diseases. The latter includes HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and HTLV-1 uveitis (HU) and other diseases with unestablished associations such as arthropathy, pneumopathy, dermatitis, exocrinopathy and myositis. ATL is defined as neoplastic clonal growth of HTLV-1-infected T-cells and is characterized by unique clinical features including hypercalcemia and severe organ infiltration of leukemic cells. HAM/TSP and HU are characterized by infiltration of HTLV-1-infected lymphocytes and dysregulated production of cytokines. Four major subtypes (genotypes) of HTLV-1 have been identified, which depend more on geography than disease. No disease-specific variants or mutations have been identified to date. A viral transcriptional regulator, Tax, regulates virus and cellular gene expression through binding to transcription factors or other cytoplasmic cellular molecules. Aberrant expression of cellular genes will affect fundamental cellular functions. The interaction between HTLV-1-infected cells and different kinds of cells in the host appears to be one of the basic mechanisms underlying the development of HTLV-1-associated diseases. This interaction may play a major role in determining tumorigenicity and in forming clinical features of the disease. Increased provirus load found in patients with HAM/TSP and HU results from clonal expansion of the HTLV-1-infected T-cells, which has been implicated in the pathogenesis of HTLV-1-associated diseases. Regulatory mechanisms of clonal growth remain unknown. Efforts to characterize functions of the viral proteins and the virus-infected cells and to understand the natural history of the HTLV-1-infection are required to determine the mechanisms of HTLV-1 viral pathogenesis.