Human T lymphotropic virus type 1 accessory protein p12I modulates calcium-mediated cellular gene expression and enhances p300 expression in T lymphocytes

Amrithraj Nair, Bindhu Michael, Hajime Hiraragi, Soledad Fernandez, Gerold Feuer, Kathleen Boris-Lawrie, Michael Dale Lairmore

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Human T-lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T cell leukemia/lymphoma (ATLL), an aggressive CD4+ T lymphocyte malignancy. Activation of T lymphocytes is required for effective retroviral integration into the host cell genome and subsequent viral replication, but the molecular mechanisms involved in HTLV-1-mediated T cell activation remain unclear. HTLV-1 encodes various accessory proteins such as P12I, which has been demonstrated to be critical for HTLV-1 infectivity in vivo in rabbits and in vitro in quiescent primary human T lymphocytes. This hydrophobic protein localizes in the endoplasmic reticulum, increases intracellular calcium, and activates nuclear factor of activated T cell-mediated transcription. To further elucidate the role of p12I in regulation of cellular gene expression, we performed gene array analysis on stable p12I- espressing Jurkat T cells, using Affymetrix U133A arrays. Our data indicate that p12I altered the expression of genes associated with a network of interrelated pathways including T cell signaling, cell proliferation, and apoptosis. Expression of several calcium-regulated genes was found to be altered by p12I, consistent with known properties of the viral protein. Gene array findings were confirmed by semiquantitative RT-PCR in Jurkat T cells and primary CD4+ T lymphocytes. Furthermore, dose-dependent expression of P12I in Jurkat T cells resulted in significant increases in p300 and p300-dependent transcription. This is the first report of a viral protein influencing the transcription of p300, a rate-limiting coadapter critical in HTLV-1-mediated T cell activation. Collectively, our data strongly indicate that HTLV-1 p12i modulates cellular gene expression patterns to hasten the activation of T lymphocytes and thereby promote efficient viral infection.

Original languageEnglish (US)
Pages (from-to)273-284
Number of pages12
JournalAIDS Research and Human Retroviruses
Volume21
Issue number4
DOIs
StatePublished - Apr 2005
Externally publishedYes

Fingerprint

Calcium
T-Lymphocytes
Human T-lymphotropic virus 1
Gene Expression
Jurkat Cells
Viral Proteins
Human T-lymphotropic virus 1 p12I protein
Genes
NFATC Transcription Factors
Adult T Cell Leukemia Lymphoma
Viral Genome
Gene Expression Regulation
Virus Diseases
Endoplasmic Reticulum
Proteins
Cell Proliferation
Apoptosis
Rabbits
Polymerase Chain Reaction
Neoplasms

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Human T lymphotropic virus type 1 accessory protein p12I modulates calcium-mediated cellular gene expression and enhances p300 expression in T lymphocytes. / Nair, Amrithraj; Michael, Bindhu; Hiraragi, Hajime; Fernandez, Soledad; Feuer, Gerold; Boris-Lawrie, Kathleen; Lairmore, Michael Dale.

In: AIDS Research and Human Retroviruses, Vol. 21, No. 4, 04.2005, p. 273-284.

Research output: Contribution to journalArticle

Nair, Amrithraj ; Michael, Bindhu ; Hiraragi, Hajime ; Fernandez, Soledad ; Feuer, Gerold ; Boris-Lawrie, Kathleen ; Lairmore, Michael Dale. / Human T lymphotropic virus type 1 accessory protein p12I modulates calcium-mediated cellular gene expression and enhances p300 expression in T lymphocytes. In: AIDS Research and Human Retroviruses. 2005 ; Vol. 21, No. 4. pp. 273-284.
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