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

Garret C. Newbound, John P. O'Rourke, Nathaniel D. Collins, James De Wille, Michael Dale Lairmore

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

HTLV-I is the etiologic agent of adult T-cell leukemia/lymphoma and is associated with tropical spastic paraparesis/HTLV-I-associated myelopathy. Following integration into the host cell genome, HTLV-I replication is regulated by both host and vital 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 cyclic adenosine monophosphate (cAMP) response element binding (CREB)/activating transcription factor 1 (ATF-1) family of transcription factors bind three 21-bp repeats (Tax-responsive element-1, or TRE-1) within the viral promoter and are important for basal and Tax-mediated transcription. Using mitogen stimulated and quiescent peripheral blood mononuclear cells (PBMC) and Jurkat cells, we compared differences in basal transcription and amounts and binding of transcription factors with TRE-1. We demonstrate that amounts of transcriptionally active phosphorylated CREB protein (P-CREB) differ between activated PBMC and Jurkat cells. Following stimulation, P-CREB levels remain elevated in PBMC for up to 24 hours whereas CREB is dephosphorylated in Jurkat cells within 4 hours following stimulation. The differences in P-CREB levels between PBMC and Jurkat cells were directly correlated with basal transcription of HTLV-I in the two cell types. Using electrophoretic mobility shift assays, we determined that the pattern of band migration differed between the two cell types. These data demonstrate that PBMC differentially regulate basal HTLV-I transcription compared with Jurkat T cells, and this differential regulation is due, in part to differential phosphorylation and binding of CREB/ATF-1 to TRE-1 in the HTLV-I promoter. We demonstrate the utility of using primary lymphocyte models to study HTLV-I transcription in the context of cell signaling and suggest that activated PBMC maintain elevated levels of P-CREB, which promote basal HTLV-I transcription and enhance viral persistence in vivo.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalJournal of Acquired Immune Deficiency Syndromes and Human Retrovirology
Volume20
Issue number1
StatePublished - Jan 1 1999
Externally publishedYes

Fingerprint

Human T-lymphotropic virus 1
Jurkat Cells
Response Elements
Blood Cells
Cyclic AMP Response Element-Binding Protein
T-Lymphocytes
Activating Transcription Factor 1
Transcription Factors
tax Gene Products
Tropical Spastic Paraparesis
Adult T Cell Leukemia Lymphoma
Electrophoretic Mobility Shift Assay
Mitogens
Cyclic AMP
Phosphorylation
Genome
Lymphocytes

Keywords

  • Cell signaling
  • CREB/ATF- 1/CREM
  • HTLV-I
  • Jurkat cells
  • Peripheral blood mononuclear cells
  • Transcription

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Virology

Cite this

Comparison of HTLV-I basal transcription and expression of CREB/ATF- 1/CREM family members in peripheral blood mononuclear cells and Jurkat T cells. / Newbound, Garret C.; O'Rourke, John P.; Collins, Nathaniel D.; De Wille, James; Lairmore, Michael Dale.

In: Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology, Vol. 20, No. 1, 01.01.1999, p. 1-10.

Research output: Contribution to journalArticle

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