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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. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-04-1406v1 106/9/3090    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chuang, H.-C. Articles by Su, I.-J. Search for Related Content PubMed PubMed Citation Articles by Chuang, H.-C. Articles by Su, I.-J. Related Collections Immunobiology Gene Expression Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY 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 From the Divisions of Clinical Research and Cancer Research, National Health Research Institutes, Taipei, Taiwan; the Institute of Basic Medical Sciences, the Department of Microbiology and Immunology, and the Department of Pathology, College of Medicine, National Cheng Kung University, Tainan, Taiwan. The primary infection of Epstein-Barr virus (EBV) may result in fatal infectious mononucleosis or hemophagocytic syndrome (HPS) in 2 diseases; that is, X-linked lymphoproliferative disorder (XLP) and hemophagocytic lymphohistiocytosis (HLH). XLP is linked to mutations of the SAP/SH2D1A gene with dysregulated T-cell activation in response to EBV infection. Patients with sporadic HLH, however, usually have no mutation of the SAP/SH2D1A gene, and EBV latent membrane protein-1 (LMP1) can up-regulate 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 signaling lymphocyte activation molecule (SLAM)–associated protein (SAP) and LMP1-mediated pathways to explain the common pathogenesis of HPS. In this study, no mutation of the SAP/SH2D1A gene at exon 2/3 was detected in 7 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 the TNF receptor–associated factor (TRAF)2,5/nuclear factor B (NF-B) pathway, since dominantnegative TRAF2/5 and NF-B inhibitor could rescue SAP expression and downregulate IFN-. Although HLH is genetically distinct from XLP, our data suggest that both diseases share a common signal pathway, through either the mutation or LMP1-mediated suppression of the 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. 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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]

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