Pathogenesis and treatment of human T-cell leukemia virus infection

Abstract

The pathogenesis of human T-cell leukemia virus (HTLV)-induced adult T-cell leukemia-lymphoma (ATLL) was explored using an infectious molecular viral clone and a transgenic mouse model. Activation of nuclear factor-kappaB by the HTLV transcriptional transactivator protein Tax was found to be important for lymphocyte immortalization and tumorigenesis. Interferon-gamma regulates tumor development owing primarily to angiostatic effects. Translational clinical studies of chemotherapy, interferon-alpha, and nucleoside reverse transcriptase inhibitors have also assisted in identifying the pathogenic features of ATLL.

Fig. 1

The HTLV genome is shown with the functions of the viral gene products indicated. The Tax protein is the principal oncogenic protein of the virus, which functions as a transcriptional trans activator of the indicated target genes, via interactions with the cellular transcription factors CREB/ATF, SRF, NF-κB, SP1, EGR-1 and bHLH proteins.