國家衛生研究院 NHRI:Item 3990099045/2109

NHRI > National Institute of Infectious Diseases and Vaccinology > Ih-Jen Su(2002-2015) > Periodical Articles > Item 3990099045/2109

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/2109

Title:	Epstein-Barr virus LMP1 inhibits the expression of SAP gene and upregulates Th1 cytokines in the pathogenesis of hemophagocytic syndrome
Authors:	Chuang, HC;Lay, JD;Hsieh, WC;Wang, HC;Chang, Y;Chuang, SE;Su, IJ
Contributors:	Division of Clinical Research;National Institute of Cancer Research
Abstract:	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-gamma (IFN-gamma). LMP1-mediated SAP/ERK/IFN-gamma signals appear to act via the TNF receptor-associated factor (TRAF)2,5/nuclear factor kappa B (NF-kappa B) pathway, since dominant-negative TRAF2/5 and NF-kappa B inhibitor could rescue SAP expression and down-regulate IFN-gamma. 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.
Keywords:	Hematology
Date:	2005-11-01
Relation:	Blood. 2005 Nov;106(9):3090-3096.
Link to:	http://dx.doi.org/10.1182/blood-2005-04-1406
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0006-4971&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000232917400034
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=27644592071
Appears in Collections:	[Ih-Jen Su(2002-2015)] Periodical Articles [Yao Chang] Periodical Articles [Shuang-En Chuang] Periodical Articles [Huai-Chia Chuang] Periodical Articles

Files in This Item:

File	Description	Size	Format
000232917400034.pdf		448Kb	Adobe PDF	980	View/Open

Loading...