Comparison of HTLV-I basal transcription and expression of CREB/ATF-1/CREMfamily members in peripheral blood mononuclear cells and Jurkat T cells

HTLV-I is the etiologic agent of adult T-cell leukemia/lymphoma and is asso ciated with tropical spastic paraparesis/HTLV-I-associated myelopathy. Foll owing integration into the host cell genome, HTLV-I replication is regulate d by both host and viral mechanisms that control transcription. Low levels of viral transcription (basal transcription) occur before expression of the virally encoded Tax protein (Tax-mediated transcription). Members of the c yclic adenosine monophosphate (cAMP) response element binding (CREB)/activa ting transcription factor 1 (ATF-I) family of transcription factors bind th ree 21-bp repeats (Tax-responsive element-1, or TRE-1) within the viral pro moter and are important for basal and Tax-mediated transcription. Using mit ogen stimulated and quiescent peripheral blood mononuclear cells (PBMC) and Jurkat cells, we compared differences in basal transcription and amounts a nd binding of transcription factors with TRE-1. We demonstrate that amounts of transcriptionally active phosphorylated CREB protein (P-CREB) differ be tween activated PBMC and Jurkat cells. Following stimulation, P-CREB levels remain elevated in PBMC for up to 24 hours whereas CREB is dephosphorylate d in Jurkat cells within 4 hours following stimulation. The differences in P-CREB levels between PBMC and Jurkat cells were directly correlated with b asal transcription of HTLV-I in the two cell types. Using electrophoretic m obility shift assays, we determined that the pattern of band migration diff ered between the two cell types. These data demonstrate that PBMC different ially regulate basal HTLV-I transcription compared with Jurkat T cells, and this differential regulation is due, in part to differential phosphorylati on and binding of CREB/ATF-1 to TRE-1 in the HTLV-I promoter. We demonstrat e the utility of using primary lymphocyte models to study HTLV-I transcript ion in the context of cell signaling and suggest that activated PBMC mainta in elevated levels of P-CREB, which promote basal HTLV-I transcription and enhance viral persistence in vivo.