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 polypyrimidine motif [C(N)(4-14)] downstream of the mRNA cap structure. T-cell clones naturally infected with transcriptionally active human T-cell leukaemia virus, type I (HTLV-I) undergo autologous proliferation; this phenotype is inhibited by rapamycin but not FK506, which reverses the rapamycin effect. Within the R region of the HTLV-I 5' long terminal repeat (LTR) there are seven polypyrimidine motifs. We sought to determine if these were involved in the sensitivity of proliferation to the presence of rapamycin. Here we illustrate the generation of an in vitro model of this rapamycin-sensitivity and the analysis of LTR mutants which were created to determine the importance of the polypyrimidine motifs. Reporter gene assays suggest the effect is independent of the polypyrimidine motifs in the virus leader sequence.
Rose
Nicola J
NJ
Department of Medicine, University of Cambridge, Level 5, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK1.
Lever
Andrew M L
AML
Department of Medicine, University of Cambridge, Level 5, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK1.
D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002455:Cell Division / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D016370:Gene Products, rex / Q000235:genetics / Q000378:metabolism; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism; D017930:Genes, Reporter / Q000235:genetics; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D019169:Jurkat Cells; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D020123:Sirolimus / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D016559:Tacrolimus / Q000494:pharmacology; D020079:Terminal Repeat Sequences / Q000235:genetics*; D014162:Transfection
D016370:Gene Products, rex; D016356:Gene Products, tax; D007166:Immunosuppressive Agents; D020123:Sirolimus; D016559:Tacrolimus