IL-2 withdrawal induces HTLV-1 expression through p38 activation in ATL cell lines

Abstract 

Expression of human T-cell leukemia virus type-1 (HTLV-1) in adult T-cell leukemia (ATL) cells is known to be marginal in vivo and inducible in short-term culture. In this study, we demonstrated that withdrawal of interleukin (IL)-2 from IL-2-dependent ATL cell lines resulted in induction of HTLV-1 mRNA and protein expression, and that viral induction was associated with phosphorylation of the stress kinase p38 and its downstream CREB. Pharmacological inhibitors of the p38 pathway suppressed viral expression induced by IL-2 depletion. These results indicate that the stress-induced p38 pathway might up-regulate HTLV-1 gene expression through at least CREB activation.

Abbreviations: ATL, adult T-cell leukemia, CREB, cAMP responsive element binding protein, Erk, extracellular signal-regulated protein kinase, FBS, fetal bovine serum, HTLV-1, human T-cell leukemia virus-1, IL-2, interleukin 2, JNK, Jun N-terminal kinase, LTR, long-terminal repeat, MFI, mean fluorescence intensity, PBS, phosphate-buffered saline

Keywords: HTLV-1, p38, Expression, CREB, IL-2