Human T cell leukemia virus type I Tax activates CD40 gene expression via the NF-kappa B pathway

Edward W. Harhaj, Nicole S. Harhaj, Christian Grant, Kate Mostoller, Timothy Alefantis, Shao Cong Sun, Brian Wigdahl

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The human T cell leukemia virus type I (HTLV-I) is an oncogenic retrovirus that is etiologically linked to the genesis of adult T cell leukemia (ATL) as well as HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Emerging evidence suggests that the pathogenicity of HTLV-I involves deregulated activation of immune cells, especially T lymphocytes, although the underlying mechanism remains unclear. In this study, we demonstrate that HTLV-I Tax induces the aberrant expression of CD40, a member of the tumor necrosis factor receptor (TNFR) family that plays an important role in lymphocyte activation and differentiation. In a panel of HTLV-I-transformed T cell lines analyzed, CD40 expression was highly elevated compared to HTLV-I-negative T cells. Using Tax mutants and a genetically manipulated T cell system, we demonstrated that Tax-induced CD40 expression required the NF-κB signaling pathway. In addition, ligation of CD40 on T cells with recombinant CD40L elicited NF-κB activation, suggesting that the CD40 pathway is intact and may participate in a positive regulatory loop in T cells. CD40 ligation strongly synergized with Tax to activate NF-κB, suggesting that CD40 signals may costimulate Tax-mediated NF-κB activation, particularly when Tax is expressed at low levels. Collectively, these results indicate that CD40 is a novel Tax-regulated gene, and the regulation of CD40 by Tax may play a role in cellular activation and HTLV-I-induced disease pathogenesis.

Original languageEnglish (US)
Pages (from-to)145-158
Number of pages14
JournalVirology
Volume333
Issue number1
DOIs
StatePublished - Mar 1 2005

Fingerprint

Human T-lymphotropic virus 1
NF-kappa B
Gene Expression
T-Lymphocytes
Ligation
pX Genes
Tropical Spastic Paraparesis
Adult T Cell Leukemia Lymphoma
CD40 Ligand
Transformed Cell Line
Tumor Necrosis Factor Receptors
Spinal Cord Diseases
Retroviridae
Lymphocyte Activation
Virulence

All Science Journal Classification (ASJC) codes

  • Virology

Cite this

Harhaj, E. W., Harhaj, N. S., Grant, C., Mostoller, K., Alefantis, T., Sun, S. C., & Wigdahl, B. (2005). Human T cell leukemia virus type I Tax activates CD40 gene expression via the NF-kappa B pathway. Virology, 333(1), 145-158. https://doi.org/10.1016/j.virol.2004.12.008
Harhaj, Edward W. ; Harhaj, Nicole S. ; Grant, Christian ; Mostoller, Kate ; Alefantis, Timothy ; Sun, Shao Cong ; Wigdahl, Brian. / Human T cell leukemia virus type I Tax activates CD40 gene expression via the NF-kappa B pathway. In: Virology. 2005 ; Vol. 333, No. 1. pp. 145-158.
@article{48c073117dc44e6c98e5214cc94dbf94,
title = "Human T cell leukemia virus type I Tax activates CD40 gene expression via the NF-kappa B pathway",
abstract = "The human T cell leukemia virus type I (HTLV-I) is an oncogenic retrovirus that is etiologically linked to the genesis of adult T cell leukemia (ATL) as well as HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Emerging evidence suggests that the pathogenicity of HTLV-I involves deregulated activation of immune cells, especially T lymphocytes, although the underlying mechanism remains unclear. In this study, we demonstrate that HTLV-I Tax induces the aberrant expression of CD40, a member of the tumor necrosis factor receptor (TNFR) family that plays an important role in lymphocyte activation and differentiation. In a panel of HTLV-I-transformed T cell lines analyzed, CD40 expression was highly elevated compared to HTLV-I-negative T cells. Using Tax mutants and a genetically manipulated T cell system, we demonstrated that Tax-induced CD40 expression required the NF-κB signaling pathway. In addition, ligation of CD40 on T cells with recombinant CD40L elicited NF-κB activation, suggesting that the CD40 pathway is intact and may participate in a positive regulatory loop in T cells. CD40 ligation strongly synergized with Tax to activate NF-κB, suggesting that CD40 signals may costimulate Tax-mediated NF-κB activation, particularly when Tax is expressed at low levels. Collectively, these results indicate that CD40 is a novel Tax-regulated gene, and the regulation of CD40 by Tax may play a role in cellular activation and HTLV-I-induced disease pathogenesis.",
author = "Harhaj, {Edward W.} and Harhaj, {Nicole S.} and Christian Grant and Kate Mostoller and Timothy Alefantis and Sun, {Shao Cong} and Brian Wigdahl",
year = "2005",
month = "3",
day = "1",
doi = "10.1016/j.virol.2004.12.008",
language = "English (US)",
volume = "333",
pages = "145--158",
journal = "Virology",
issn = "0042-6822",
publisher = "Academic Press Inc.",
number = "1",

}

Harhaj, EW, Harhaj, NS, Grant, C, Mostoller, K, Alefantis, T, Sun, SC & Wigdahl, B 2005, 'Human T cell leukemia virus type I Tax activates CD40 gene expression via the NF-kappa B pathway', Virology, vol. 333, no. 1, pp. 145-158. https://doi.org/10.1016/j.virol.2004.12.008

Human T cell leukemia virus type I Tax activates CD40 gene expression via the NF-kappa B pathway. / Harhaj, Edward W.; Harhaj, Nicole S.; Grant, Christian; Mostoller, Kate; Alefantis, Timothy; Sun, Shao Cong; Wigdahl, Brian.

In: Virology, Vol. 333, No. 1, 01.03.2005, p. 145-158.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Human T cell leukemia virus type I Tax activates CD40 gene expression via the NF-kappa B pathway

AU - Harhaj, Edward W.

AU - Harhaj, Nicole S.

AU - Grant, Christian

AU - Mostoller, Kate

AU - Alefantis, Timothy

AU - Sun, Shao Cong

AU - Wigdahl, Brian

PY - 2005/3/1

Y1 - 2005/3/1

N2 - The human T cell leukemia virus type I (HTLV-I) is an oncogenic retrovirus that is etiologically linked to the genesis of adult T cell leukemia (ATL) as well as HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Emerging evidence suggests that the pathogenicity of HTLV-I involves deregulated activation of immune cells, especially T lymphocytes, although the underlying mechanism remains unclear. In this study, we demonstrate that HTLV-I Tax induces the aberrant expression of CD40, a member of the tumor necrosis factor receptor (TNFR) family that plays an important role in lymphocyte activation and differentiation. In a panel of HTLV-I-transformed T cell lines analyzed, CD40 expression was highly elevated compared to HTLV-I-negative T cells. Using Tax mutants and a genetically manipulated T cell system, we demonstrated that Tax-induced CD40 expression required the NF-κB signaling pathway. In addition, ligation of CD40 on T cells with recombinant CD40L elicited NF-κB activation, suggesting that the CD40 pathway is intact and may participate in a positive regulatory loop in T cells. CD40 ligation strongly synergized with Tax to activate NF-κB, suggesting that CD40 signals may costimulate Tax-mediated NF-κB activation, particularly when Tax is expressed at low levels. Collectively, these results indicate that CD40 is a novel Tax-regulated gene, and the regulation of CD40 by Tax may play a role in cellular activation and HTLV-I-induced disease pathogenesis.

AB - The human T cell leukemia virus type I (HTLV-I) is an oncogenic retrovirus that is etiologically linked to the genesis of adult T cell leukemia (ATL) as well as HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Emerging evidence suggests that the pathogenicity of HTLV-I involves deregulated activation of immune cells, especially T lymphocytes, although the underlying mechanism remains unclear. In this study, we demonstrate that HTLV-I Tax induces the aberrant expression of CD40, a member of the tumor necrosis factor receptor (TNFR) family that plays an important role in lymphocyte activation and differentiation. In a panel of HTLV-I-transformed T cell lines analyzed, CD40 expression was highly elevated compared to HTLV-I-negative T cells. Using Tax mutants and a genetically manipulated T cell system, we demonstrated that Tax-induced CD40 expression required the NF-κB signaling pathway. In addition, ligation of CD40 on T cells with recombinant CD40L elicited NF-κB activation, suggesting that the CD40 pathway is intact and may participate in a positive regulatory loop in T cells. CD40 ligation strongly synergized with Tax to activate NF-κB, suggesting that CD40 signals may costimulate Tax-mediated NF-κB activation, particularly when Tax is expressed at low levels. Collectively, these results indicate that CD40 is a novel Tax-regulated gene, and the regulation of CD40 by Tax may play a role in cellular activation and HTLV-I-induced disease pathogenesis.

UR - http://www.scopus.com/inward/record.url?scp=13544261552&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=13544261552&partnerID=8YFLogxK

U2 - 10.1016/j.virol.2004.12.008

DO - 10.1016/j.virol.2004.12.008

M3 - Article

C2 - 15708600

AN - SCOPUS:13544261552

VL - 333

SP - 145

EP - 158

JO - Virology

JF - Virology

SN - 0042-6822

IS - 1

ER -