Distinct gene expression signatures induced by viral transactivators of different HTLV-1 subgroups that confer a different risk of HAM/TSP.
Distinct gene expression signatures induced by viral transactivators of different HTLV-1 subgroups that confer a different risk of HAM/TSP.
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DOI：
10.1186/s12977-018-0454-x
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发表时间：
2018-11-06
期刊：
影响因子：
3.3
通讯作者：
Saito M
中科院分区：
文献类型：
--
作者：
Naito T;Yasunaga JI;Mitobe Y;Shirai K;Sejima H;Ushirogawa H;Tanaka Y;Nakamura T;Hanada K;Fujii M;Matsuoka M;Saito M
在人类T细胞白血病病毒1型（HTLV-1）感染个体中，HTLV-1亚型（a亚组或b亚组）与日本人群HAM/TSP风险之间存在关联。为了研究HTLV-1亚群在病毒发病机制中的作用，我们利用微阵列分析、报告基因分析和病毒-宿主蛋白-蛋白相互作用评估研究了亚群特异性病毒转录调控因子Tax和HBZ的功能差异。(1)在诱导启动子的控制下，表达Tax或HBZ蛋白各亚群的Jurkat et- on人t细胞的转录变化揭示了不同的靶基因谱；(2) HBZ诱导的差异调控基因数量是Tax诱导的差异调控基因数量的2 ~ 3倍；(3) Tax和HBZ诱导不同种类的非编码rna （ncRNAs）的表达；(4)趋化因子CXCL10，已被提出作为HAM/TSP的预后生物标志物，在体外以及从HAM/TSP患者获得的未处理（离体）pbmc中，被a亚组Tax （Tax- a）比b亚组Tax （Tax- b）更有效地诱导；(5)报告基因检测表明，虽然htlv -1阴性的人t细胞系中瞬时表达的Tax通过NF-κB途径激活CXCL10基因启动子，但各亚群的Tax激活CXCL10启动子的能力没有差异；然而，(6)染色质免疫沉淀实验显示，含有taxa的三元配合物比含有Tax-B的三元配合物更有效地招募到含有两个NF-κB结合位点的CXCL10启动子区域。我们的研究结果表明，不同的HTLV-1亚群具有不同的宿主基因表达模式。亚群特异性Tax或HBZ致病相关基因的差异表达可能与HAM/TSP的发病有关。本文的在线版本（10.1186/s12977-018-0454-x）包含补充材料，可供授权用户使用。
Among human T cell leukemia virus type 1 (HTLV-1)-infected individuals, there is an association between HTLV-1 tax subgroups (subgroup-A or subgroup-B) and the risk of HAM/TSP in the Japanese population. To investigate the role of HTLV-1 subgroups in viral pathogenesis, we studied the functional difference in the subgroup-specific viral transcriptional regulators Tax and HBZ using microarray analysis, reporter gene assays, and evaluation of viral-host protein–protein interaction. (1) Transcriptional changes in Jurkat Tet-On human T-cells that express each subgroup of Tax or HBZ protein under the control of an inducible promoter revealed different target gene profiles; (2) the number of differentially regulated genes induced by HBZ was 2–3 times higher than that induced by Tax; (3) Tax and HBZ induced the expression of different classes of non-coding RNAs (ncRNAs); (4) the chemokine CXCL10, which has been proposed as a prognostic biomarker for HAM/TSP, was more efficiently induced by subgroup-A Tax (Tax-A) than subgroup-B Tax (Tax-B), in vitro as well as in unmanipulated (ex vivo) PBMCs obtained from HAM/TSP patients; (5) reporter gene assays indicated that although transient Tax expression in an HTLV-1-negative human T-cell line activated the CXCL10 gene promoter through the NF-κB pathway, there was no difference in the ability of each subgroup of Tax to activate the CXCL10 promoter; however, (6) chromatin immunoprecipitation assays showed that the ternary complex containing Tax-A is more efficiently recruited onto the promoter region of CXCL10, which contains two NF-κB binding sites, than that containing Tax-B. Our results indicate that different HTLV-1 subgroups are characterized by different patterns of host gene expression. Differential expression of pathogenesis-related genes by subgroup-specific Tax or HBZ may be associated with the onset of HAM/TSP. The online version of this article (10.1186/s12977-018-0454-x) contains supplementary material, which is available to authorized users.
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影响因子：
5.2
作者：
Ciminale V;Rende F;Bertazzoni U;Romanelli MG
通讯作者：
Romanelli MG
影响因子：
6.4
作者：
Furukawa, Y;Yamashita, M;Osame, M
通讯作者：
Osame, M
DOI：
10.1073/pnas.77.12.7415
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
POIESZ, BJ;RUSCETTI, FW;GALLO, RC
通讯作者：
GALLO, RC
DOI：
10.1073/pnas.91.9.3584
发表时间：
1994-04-26
影响因子：
11.1
作者：
HIRAI, H;SUZUKI, T;YOSHIDA, M
通讯作者：
YOSHIDA, M
影响因子：
3.3
作者：
Montanheiro, Patricia;Posada Vergara, Maria Paulina;Casseb, Jorge
通讯作者：
Casseb, Jorge