A computational profiling of changes in gene expression and transcription factors induced by vFLIP K13 in primary effusion lymphoma.
A computational profiling of changes in gene expression and transcription factors induced by vFLIP K13 in primary effusion lymphoma.
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DOI：
10.1371/journal.pone.0037498
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Chaudhary PM
中科院分区：
文献类型：
--
作者：
Punj V;Matta H;Chaudhary PM
卡波西肉瘤相关疱疹病毒（KSHV）感染与原发性渗出性淋巴瘤（PEL）的发生有关，这是一种罕见的淋巴组织增生性疾病，其特征是大多数B细胞标志物表达缺失和体腔积液。PEL的这种独特的临床表现归因于其独特的血浆蛋白酶基因表达谱，其显示参与炎症、粘附和侵袭的基因的过表达。KSHV编码的潜伏蛋白vFLIP K13先前已显示促进PEL细胞的存活和增殖。在这项研究中，我们采用基因阵列分析来表征K13对PEL衍生的BCBL 1细胞中全局基因表达的影响，该细胞内源性表达可忽略不计的K13。我们证明K13上调了许多参与细胞因子信号传导、细胞死亡、粘附、炎症和免疫反应的NF-κB应答基因的表达，包括参与替代NF-κB途径的两个NF-κB亚基RELB和NF KB 2。相反，B细胞标记物CD 19是K13下调的基因之一。与人血管内皮细胞中K13诱导的基因的比较显示，尽管在两种细胞类型中K13诱导的基因之间存在相当大的重叠，但趋化因子基因优先在HUVEC中诱导，只有少数例外，如RANTES/CCL 5，其在两种细胞类型中均被诱导。功能研究证实K13通过NF-κB途径激活RANTES/CCL 5启动子。总的来说，我们的研究结果表明，K13可能有助于独特的基因表达谱，免疫表型和临床表现，KSHV相关的PEL的特点。
Infection with Kaposi's sarcoma associated herpesvirus (KSHV) has been linked to the development of primary effusion lymphoma (PEL), a rare lymphoproliferative disorder that is characterized by loss of expression of most B cell markers and effusions in the body cavities. This unique clinical presentation of PEL has been attributed to their distinctive plasmablastic gene expression profile that shows overexpression of genes involved in inflammation, adhesion and invasion. KSHV-encoded latent protein vFLIP K13 has been previously shown to promote the survival and proliferation of PEL cells. In this study, we employed gene array analysis to characterize the effect of K13 on global gene expression in PEL-derived BCBL1 cells, which express negligible K13 endogenously. We demonstrate that K13 upregulates the expression of a number of NF-κB responsive genes involved in cytokine signaling, cell death, adhesion, inflammation and immune response, including two NF-κB subunits involved in the alternate NF-κB pathway, RELB and NFKB2. In contrast, CD19, a B cell marker, was one of the genes downregulated by K13. A comparison with K13-induced genes in human vascular endothelial cells revealed that although there was a considerable overlap among the genes induced by K13 in the two cell types, chemokines genes were preferentially induced in HUVEC with few exceptions, such as RANTES/CCL5, which was induced in both cell types. Functional studies confirmed that K13 activated the RANTES/CCL5 promoter through the NF-κB pathway. Taken collectively, our results suggest that K13 may contribute to the unique gene expression profile, immunophenotype and clinical presentation that are characteristics of KSHV-associated PEL.
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DOI：
10.1084/jem.20031467
发表时间：
2004-04-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Guasparri I;Keller SA;Cesarman E
通讯作者：
Cesarman E
影响因子：
16.8
作者：
Appay, V;Rowland-Jones, SL
通讯作者：
Rowland-Jones, SL
趋化因子在调节慢性病毒感染过程中调节CD8 T细胞反应的作用。
影响因子：
6.7
作者：
Crawford A;Angelosanto JM;Nadwodny KL;Blackburn SD;Wherry EJ
通讯作者：
Wherry EJ
影响因子：
64.8
作者：
Karnoub, Antoine E.;Dash, Ajeeta B.;Weinberg, Robert A.
通讯作者：
Weinberg, Robert A.
影响因子：
4.8
作者：
Hideshima, T;Chauhan, D;Anderson, KC
通讯作者：
Anderson, KC