Journal article
Human T cell leukemia virus type I Tax activates CD40 gene expression via the NF-kappa B pathway
Virology (New York, N.Y.), v 333(1), pp 145-158
2005
PMID: 15708600
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- Human T cell leukemia virus type I Tax activates CD40 gene expression via the NF-kappa B pathway
- Creators
- Edward W Harhaj - Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami School of Medicine, Room 503, Papanicolaou Building, 1550 NW 10th Avenue, Miami, FL 33136, USANicole S Harhaj - Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami School of Medicine, Room 503, Papanicolaou Building, 1550 NW 10th Avenue, Miami, FL 33136, USAChristian Grant - Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USAKate Mostoller - Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USATimothy Alefantis - Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USAShao-Cong Sun - Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USABrian Wigdahl - Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
- Publication Details
- Virology (New York, N.Y.), v 333(1), pp 145-158
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000227119000014
- Scopus ID
- 2-s2.0-13544261552
- Other Identifier
- 991014878434404721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Virology