Molecular biology of human T cell leukemia virus

Human T cell leukemia virus type 1 (HTLV-1) is a horizontally transmitted virus infection of CD4+ lymphocytes which causes adult T cell leukemia-lymphoma (ATLL) and HTLV-associated myelopathy (HAM). The viral genome encodes two oncoproteins, transactivator protein (Tax) and helix basic zipper protein (HBZ), which are considered tumor initiator and maintenance factors, respectively. Tax is the primary inducer of clonal infected T cell expansion, and genetic instability. The immune response to Tax results in the selection of cells with little or no Tax expression, which have undergone genetic and epigenetic alterations that promote T cell activation, proliferation, and resistance to apoptosis. This selection of malignant cells occurs over several decades in 5% of infected individuals. Novel insights into the molecular details of each of these events has led to targeted therapies for ATLL.