Human T-cell lymphotropic virus type 1 p12I expression increases cytoplasmic calcium to enhance the activation of nuclear factor of activated T cells

Wei D Ding, Björn Albrecht, Robert E. Kelley, Natarajan Muthusamy, Seung Jae Kim, Ruth A. Altschuld, Michael D. Lairmore

Research output: Contribution to journalArticle

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Abstract

Human T-cell lymphotropic virus type 1 (HTLV-1) establishes persistent infection and is associated with lymphoproliferative or neurodegenerative diseases. As a complex retrovirus, HTLV-1 contains typical structural and enzymatic genes, as well as regulatory and accessory genes encoded in the pX region. The early events necessary for HTLV-1 to establish infection in lymphocytes, its primary target cells, remain unresolved. Recent studies have demonstrated the importance of regulatory and accessory gene products in determining this virus-host interaction. Among these, pX open reading frame I, which encodes two proteins, p12I and p27I, is required for establishing persistent infection in vivo and for infection in quiescent primary lymphocytes. In addition, p12I localizes in the endoplasmic reticulum (ER) and cis-Golgi apparatus and associates with a calcium binding protein, calreticulin. We recently reported that p12I expression induces the calcium-responsive T-cell transcription factor, nuclear factor of activated T cells (NFAT), in the presence of phorbol ester activation. Based on these studies, we hypothesize that p12I may modulate calcium release from the ER. Here, we report that p12I expression increases basal cytoplasmic calcium and concurrently diminishes calcium available for release from the ER stores. Overexpression of calreticulin, a calcium buffer protein, blocked p12I-mediated NFAT activation independently of its ability to bind p12I. Chemical inhibition studies using inhibitors of inositol 1,4,5-triphosphate receptor and calcium release-activated calcium channels suggest that inositol 1,4,5-triphosphate receptor in the ER membrane and calcium release-activated calcium channels in the plasma membrane contribute to p12I-mediated NFAT activation. Collectively, our results are the first to demonstrate the role of p12I in elevating cytoplasmic calcium, an antecedent to T-cell activation, and further support the important role of this accessory protein in the early events of HTLV-1 infection.

Original languageEnglish (US)
Pages (from-to)10374-10382
Number of pages9
JournalJournal of Virology
Volume76
Issue number20
DOIs
StatePublished - Oct 2002
Externally publishedYes

Fingerprint

Primate T-lymphotropic virus 1
NFATC Transcription Factors
Human T-lymphotropic virus 1
T-lymphocytes
Calcium
T-Lymphocytes
calcium
Endoplasmic Reticulum
endoplasmic reticulum
Calreticulin
Inositol 1,4,5-Trisphosphate Receptors
Regulator Genes
calreticulin
Infection
calcium channels
infection
Lymphocytes
TCF Transcription Factors
Proteins
Retroviridae

ASJC Scopus subject areas

  • Immunology

Cite this

Human T-cell lymphotropic virus type 1 p12I expression increases cytoplasmic calcium to enhance the activation of nuclear factor of activated T cells. / Ding, Wei D; Albrecht, Björn; Kelley, Robert E.; Muthusamy, Natarajan; Kim, Seung Jae; Altschuld, Ruth A.; Lairmore, Michael D.

In: Journal of Virology, Vol. 76, No. 20, 10.2002, p. 10374-10382.

Research output: Contribution to journalArticle

Ding, Wei D ; Albrecht, Björn ; Kelley, Robert E. ; Muthusamy, Natarajan ; Kim, Seung Jae ; Altschuld, Ruth A. ; Lairmore, Michael D. / Human T-cell lymphotropic virus type 1 p12I expression increases cytoplasmic calcium to enhance the activation of nuclear factor of activated T cells. In: Journal of Virology. 2002 ; Vol. 76, No. 20. pp. 10374-10382.
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AU - Albrecht, Björn

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AU - Muthusamy, Natarajan

AU - Kim, Seung Jae

AU - Altschuld, Ruth A.

AU - Lairmore, Michael D.

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