| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
1) Human T cell leukemia virus type 1 (HTLV-1) and type 2 (HTLV-2) are retroviruses with similar biological properties. HTLV-1 is the causative agent of an aggressive T cell leukemia, whereas HTLV-2 has only been associated with a few cases of lymphoproliferative disorders. We show that HTLV-2 Tax2 transformed a Rat-1 fibroblast cell line to form colonies in soft agar, but the size and number of the colonies were less than those of HTLV-1 Tax1. Chimefic Tax protein showed that the C-terminal 300-353 amino acid was responsible for the high transforming activity of Tax1. Our results showed that Tax2 has a lower transforming activity than Tax1, and suggest that the high transforming activity of Tax1 is involved in the leukemogenic property of HTLV-1.
2) HTLV-1 is exclusively detected in CD45RO+ T-cells in infected individuals, but CD45RO is weakly expressed in HTLV-1-transformed T-cell lines in vitro. Flow-cytometry showed that only two out of eight interleukin(IL)-2-independent HTLV 1-transformed T-cell lines expressed CD45RO, whereas all five IL-2-dependent ones expressed CD45RO, and the level of expression was higher in IL-2-dependent than in IL-2-independent cells. Using western blotting, we showed that IL-2-dependent HTLV-1-transformed T-cell lines expressed a lower level of expression of Tax1 than IL-2-independent ones, and that the level of expression correlated inversely with that of CD45RO. Our results suggest that CD45RO+ Tax-low IL-2-dependent T-cell lines in vitro correspond to the persistent HTLV-1-infected cells in vivo, and HTLV-1-infected cells in vivo are immortalized in IL-2-dependent manner.
3) Tax induced the expression of cyclin D1, D2 and bcl-xl in T-cell lines. Moreover, the induction of these genes was well correlated with the IL-2-independent growth of mouse T-cell lines. These results suggest that Tax-indcued expression of cyclin D1, D2 and bcl-xl play roles in the inhibition of the apoptosis and cell cycle promotion in HTLV-1-infected T-cells.
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