Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia and lymphoma, an aggressive clonal malignancy of human CD4-bearing T lymphocytes. HTLV-2, although highly related to HTLV-1 at the molecular level, has not been conclusively linked to development of lymphoproliferative disorders. Differences between the biological activities of the respective tax gene products (Tax1 and Tax2) may be one factor which accounts for the differential pathogenicities associated with infection. To develop an in vitro model to investigate and compare the effects of constitutive expression of Tax1 and Tax2, Jurkat T-cell lines were infected with lentivirus vectors encoding Tax1 and Tax2 in conjunction with green fluorescent protein, and stably transduced clonal cell lines were generated by serial dilution in the absence of drug selection. Jurkat cells that constitutively express Tax1 and Tax2 (Tax1/Jurkat and Tax2/Jurkat, respectively) showed notably reduced kinetics of cellular replication, and Tax1 inhibited cellular replication to a higher degree in comparison to Tax2. Tax1 markedly activated transcription from the cdk inhibitor p21cip1/waf1 promoter in comparison to Tax2, suggesting that upregulation of p21cip1/waf1 may account for the differential inhibition of cellular replication kinetics displayed by Tax1/Jurkat and Tax2/Jurkat cells. The presence of binucleated and multinucleated cells, reminiscent of large lymphocytes with cleaved or cerebriform nuclei often seen in HTLV-1-and-2-seropositive patients, was noted in cultures expressing Tax1 and Tax2. Although Tax1 and Tax2 expression mediated elevated resistance to apoptosis in Jurkat cells after serum deprivation, Tax1 was unique in protection from apoptosis after exposure to camptothecin and etoposide, inhibitors of topoisomerase I and II, respectively. Characterization of the unique phenotypes displayed by Tax1 and Tax2 in vitro will provide information as to the relative roles of these oncoproteins and their contribution to HTLV-1 and-2 pathogenesis in vivo.

Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) is the etiologic agent of a severe and fatal lymphoproliferative disorder of helper T cells termed adult T-cell leukemia/lymphoma (ATL/ATLL). Although HTLV-1 and HTLV-2 share ca. 70% sequence homology, infection with HTLV-2 is less pathogenic in comparison to infection with HTLV-1 and has not been definitively linked to the development of lymphoproliferative disorders. The HTLV-1 and-2 Tax proteins, p40tax (Tax1) and p37tax (Tax2), share many characteristic properties of viral oncoproteins, most notably the ability to immortalize lymphocytes for growth in vitro. The HTLV-1 tax gene is invariably maintained in ATL cells, suggesting that Tax1 plays a pivotal role in the initiation of leukemogenesis. There is a lack of understanding as to the inherent differences between HTLV-1 and HTLV-2, with respect to the ability to induce leukemia, although it is speculated that the respective functions of Tax1 and Tax2 play an important role in the early processes of disease.