Seizing of T cells by human T-cell leukemia/lymphoma virus type 1.

Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) causes neoplastic transformation of human T-cells in a small number of infected individuals several years from infection. Several viral proteins act in concert to increase the responsiveness of T-cells to extracellular stimulation, modulate proapoptotic and antiapoptotic gene signals, enhance T-cell survival, and avoid immune recognition of the infected T-cells. The virus promotes T-cell proliferation by usurping several signaling pathways central to immune T-cell function. Viral proteins modulate the downstream effects of antigen stimulation and receptor-ligand interaction, suggesting that extracellular signals are important for HTLV-1 oncogenesis. Environmental factors such as chronic antigen stimulation are therefore important, as also suggested by epidemiological data. The ability of a given individual to respond to specific antigens is determined genetically. Thus, genetic and environmental factors, together with the virus, contribute to disease development. As in the case of other virus-associated cancers, HTLV-1-induced leukemia/lymphoma can be prevented by avoiding viral infection or by intervention during the asymptomatic phase with approaches able to interrupt the vicious cycle of virus-induced proliferation of a subset of T-cells. This review focuses on current knowledge of the mechanisms regulating HTLV-1 replication and the T-cell pathways that are usurped by viral proteins to induce and maintain clonal proliferation of infected T-cells in vitro. The relevance of these laboratory findings will be related to clonal T-cell proliferation and adult T-cell leukemia/lymphoma development in vivo.