T-cell control 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. Collective evidence from in vitro studies indicates that 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, such as antigen stimulation and receptor-ligand interaction, suggesting that extracellular signals are important for HTLV-1 oncogenesis. Environmental factors such as chronic antigen stimulation may therefore be of importance, as also suggested by epidemiological data. Thus genetic and environmental factors together with the virus contribute to disease development. 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. The relevance of these laboratory findings is related to clonal T-cell proliferation and adult T-cell leukemia/lymphoma development in vivo.
Franchini
Genoveffa
G
Basic Research Laboratory, National Cancer Institute, Bethesda, Maryland 20892-5055, USA. franchig@mail.nih.gov
Fukumoto
Risaku
R
Fullen
Jake R
JR
D002471:Cell Transformation, Neoplastic / Q000276:immunology; D015490:HTLV-I Infections / Q000209:etiology; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology / Q000821:virology*; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology
D014764:Viral Proteins