The rapamycin sensitivity of human T-cell leukaemia virus type I-induced T-cell proliferation is mediated independently of the polypyrimidine motifs in the 5 ' long terminal repeat

The immunosuppressant rapamycin can regulate the translation of a subset of messenger RNAs, a phenotype which has been linked to the presence of a pol ypyrimidine motif [C(N)(4-14)] downstream of the mRNA cap structure. T-cell clones naturally infected with transcriptionally active human T-cell leuka emia virus, type I (HTLV-I) undergo autologous proliferation;this phenotype is inhibited by rapamycin but not FK506, which reverses the rapamycin effe ct. Within the R region of the HTLV-I 5' long terminal repeat (LTR) there a re seven polypyrimidine motifs, We sought to determine if these were involv ed in the sensitivity of proliferation to the presence of rapamycin, Here w e illustrate the generation of an in vitro model of this rapamycin-sensitiv ity and the analysis of LTR mutants which were created to determine the imp ortance of the polypyrimidine motifs, Reporter gene assays suggest the effe ct is independent of the polypyrimidine motifs in the virus leader sequence .