|
|
Blood, 1 November 2005, Vol. 106, No. 9, pp. 3090-3096.
Prepublished online as a Blood First Edition Paper on July 7, 2005; DOI 10.1182/blood-2005-04-1406.
 Previous Article | Next Article 
Submitted April 6, 2005
Accepted June 24, 2005
Epstein-barr virus LMP1 inhibits the expression of SAP gene and upregulates Th1 cytokines in the pathogenesis of hemophagocytic syndrome
Huai-Chia Chuang, Jong-Ding Lay, Wen-Chuan Hsieh, Hui-Ching Wang, Yao Chang, Shuang-En Chuang, and Ih-Jen Su*
Division of Clinical Research, National Health Research Institutes, Taipei, Taiwan; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
Division of Cancer Research, National Health Research Institutes, Taipei, Taiwan
Division of Clinical Research, National Health Research Institutes, Taipei, Taiwan
Division of Clinical Research, National Health Research Institutes, Taipei, Taiwan; Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Pathology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
* Corresponding author; email: suihjen{at}nhri.org.tw.
The primary infection of Epstein-Barr virus (EBV) may result in fatal infectious mononucleosis or hemophagocytic syndrome (HPS) in two diseases, i.e., X-linked lymphoproliferative disorders (XLP) and hemophagocytic lymphohistiocytosis (HLH). XLP is linked to mutations of SAP/SH2D1A gene with dysregulated T cell activation in response to EBV infection. Sporadic HLH patients, however, usually have no mutation of SAP/SH2D1A gene and EBV LMP1 protein can upregulate Th1 cytokines in EBV-infected T cells. Since both diseases share common manifestations of HPS, it is important to clarify whether a cross talk exists between SAP signaling and LMP1-mediated pathways to explain the common pathogenesis of HPS. In this study, no mutation of SAP/SH2D1A gene at exon 2/3 was detected in seven HLH cases. Interestingly, EBV LMP1 could transcriptionally inhibit the expression of SAP/SH2D1A and activate downstream molecules ERK and interferon- (IFN-). LMP1-mediated SAP/ERK/IFN- signals appear to act via TRAF2,5/NF B pathway, since dominant-negative TRAF2/5 and NFB inhibitor could rescue SAP expression and downregulate IFN-. Although HLH is genetically distinct from XLP, our data suggest that both diseases share common signal pathway, through either the mutation or LMP1-mediated suppression of SAP gene, leading to overt T cell activation and enhanced Th1 cytokine secretion in response to EBV infection.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
K.-C. Chang, Y. Chang, D. Jones, and I.-J. Su
Aberrant Expression of Cyclin A Correlates With Morphogenesis of Reed-Sternberg Cells in Hodgkin Lymphoma
Am J Clin Pathol,
July 1, 2009;
132(1):
50 - 59.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Vaysberg, O. Hatton, S. L. Lambert, A. L. Snow, B. Wong, S. M. Krams, and O. M. Martinez
Tumor-derived Variants of Epstein-Barr Virus Latent Membrane Protein 1 Induce Sustained Erk Activation and c-Fos
J. Biol. Chem.,
December 26, 2008;
283(52):
36573 - 36585.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-C. Chuang, J.-M. Wang, W.-C. Hsieh, Y. Chang, and I.-J. Su
Up-Regulation of Activating Transcription Factor-5 Suppresses SAP Expression to Activate T Cells in Hemophagocytic Syndrome Associated with Epstein-Barr Virus Infection and Immune Disorders
Am. J. Pathol.,
November 1, 2008;
173(5):
1397 - 1405.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. A. Mainou, D. N. Everly Jr., and N. Raab-Traub
Unique Signaling Properties of CTAR1 in LMP1-Mediated Transformation
J. Virol.,
September 15, 2007;
81(18):
9680 - 9692.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. G. Clarkson, S. J. Simmonds, M. J. Puklavec, and M. H. Brown
Direct and Indirect Interactions of the Cytoplasmic Region of CD244 (2B4) in Mice and Humans with FYN Kinase
J. Biol. Chem.,
August 31, 2007;
282(35):
25385 - 25394.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-C. Chuang, J.-D. Lay, S.-E. Chuang, W.-C. Hsieh, Y. Chang, and I.-J. Su
Epstein-Barr Virus (EBV) Latent Membrane Protein-1 Down-Regulates Tumor Necrosis Factor-{alpha} (TNF-{alpha}) Receptor-1 and Confers Resistance to TNF-{alpha}-Induced Apoptosis in T Cells: Implication for the Progression to T-Cell Lymphoma in EBV-Associated Hemophagocytic Syndrome
Am. J. Pathol.,
May 1, 2007;
170(5):
1607 - 1617.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W.-C. Hsieh, Y. Chang, M.-C. Hsu, B.-S. Lan, G.-C. Hsiao, H.-C. Chuang, and I.-J. Su
Emergence of Anti-Red Blood Cell Antibodies Triggers Red Cell Phagocytosis by Activated Macrophages in a Rabbit Model of Epstein-Barr Virus-Associated Hemophagocytic Syndrome
Am. J. Pathol.,
May 1, 2007;
170(5):
1629 - 1639.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Mischler, G. M. Fleming, T. P. Shanley, L. Madden, J. Levine, V. Castle, A. H. Filipovich, and T. T. Cornell
Epstein-Barr Virus-Induced Hemophagocytic Lymphohistiocytosis and X-Linked Lymphoproliferative Disease: A Mimicker of Sepsis in the Pediatric Intensive Care Unit
Pediatrics,
May 1, 2007;
119(5):
e1212 - e1218.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-D. Lay, C.-C. Hong, J.-S. Huang, Y.-Y. Yang, C.-Y. Pao, C.-H. Liu, Y.-P. Lai, G.-M. Lai, A.-L. Cheng, I.-J. Su, et al.
Sulfasalazine Suppresses Drug Resistance and Invasiveness of Lung Adenocarcinoma Cells Expressing AXL
Cancer Res.,
April 15, 2007;
67(8):
3878 - 3887.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. N. Dessypris
The story of hungry macrophages
Blood,
February 15, 2006;
107(4):
1250a - 1251.
[Full Text]
[PDF]
|
|
|
|
|
