Human T-cell lymphotropic virus type 1 tax mediates enhanced transcription in CD4+ T lymphocytes

Garret C. Newbound, Janice M. Andrews, John P. O'Rourke, John N. Brady, Michael Dale Lairmore

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Abstract

Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma and is associated with a variety of immunoregulatory disorders. HTLV-1 has been shown to bind to and infect a variety of hematopoietic and nonhematopoietic cells. However, both in vivo and in vitro, the provirus is mostly detected in and preferentially transforms CD4+ T cells. The molecular mechanism that determines the CD4+ T-cell tropism of HTLV-1 has not been determined. Using cocultures of purified CD4+ and CD8+ T cells with an HTLV-1-producing cell line, we measured viral transcription by using Northern (RNA) blot analysis, protein production by using a p24 antigen capture assay and flow cytometric analysis for viral envelope, and proviral integration by using DNA slot blot analysis. We further measured HTLV-1 long terminal repeat, directed transcription in purified CD4+ and CD8+ T cells by using transient transfection assays and in vitro transcription. We demonstrate a higher rate of viral transcription in primary CD4+ T cells than in CD8+ T cells. HTLV-1 protein production was 5- to 25-fold greater in CD4+ cocultures and mRNA levels were 5-fold greater in these cultures than in the CD8+ cocultures. Transient transfection and in vitro transcription indicated a modest increase in basal transcription in CD4+ T cells, whereas there was a 20-fold increase in reporter gene activity in CD4+ T cells cotransfected with tax. These data suggest that unique or activated transcription factors, particularly Tax-responsive factors in CD4+ T cells, recognize regulatory sequences within the HTLV-1 long terminal repeat, and this mediates the observed enhanced vital transcription and ultimately the cell tropism and leukemogenic potential of the virus.

Original languageEnglish (US)
Pages (from-to)2101-2106
Number of pages6
JournalJournal of Virology
Volume70
Issue number4
StatePublished - 1996
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

Cite this

Newbound, G. C., Andrews, J. M., O'Rourke, J. P., Brady, J. N., & Lairmore, M. D. (1996). Human T-cell lymphotropic virus type 1 tax mediates enhanced transcription in CD4+ T lymphocytes. Journal of Virology, 70(4), 2101-2106.