Functional analysis of HTLV-I Tax in vivo using a rat model system

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Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL). Although the viral transactivation factor, Tax, has known to have the apparent transforming ability, the exact function of Tax for ATL development is still not clear. To understand the role of Tax in ATL development, in this study, we introduced short-interfering RNAs (siRNAs) against Tax in a rat HTLV-1 infected T cell line. Our results demonstrated that expression of siRNA targeting Tax successfully downregulated Tax expression. Repression of Tax expression was associated with resistance of the HTLV-1 infected T cells to Tax-specific cytotoxic T lymphocytes killing. This may be due to the direct effect of decreased Tax expression, because the Tax siRNA did not alter the expression of MHC-I, CD80, nor CD86. Furthermore, T cells with Tax down regulation appeared to lose the ability to develop tumors in T cell-deficient nude rats, in which the parental HTLV-1-infected cells induce ATL-like lymphoproliferative disease. These results indicated the importance of Tax both for activating host immune response against the virus and for maintaining the growth ability of infected cells in vivo. Our results provide insights into the mechanisms how the host immune system can survey and inhibit the growth of HTLV-1-infected cells during the long latent period before the onset of ATL.