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基于整合素/配体信号激活在源自HAM/TSP患者的HTLV-I感染T细胞系中产生HTLV-I

HTLV-I production based on activation of integrin/ligand signaling in HTLV-I-infected T cell lines derived from HAM/TSP patients.

作者信息

Fukushima Naomi, Nakamura Tatsufumi, Nishiura Yoshihiro, Ida Hiroaki, Aramaki Toshiyuki, Eguchi Katsumi

机构信息

Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.

出版信息

Intervirology. 2008;51(2):123-9. doi: 10.1159/000139130. Epub 2008 Jun 16.

Abstract

OBJECTIVE

Activity of integrin/ligand signaling leading to activation of small GTPases might regulate the efficiency of cell-to-cell spread of human T lymphotropic virus type I (HTLV-I) through the virological synapse. We compared both activity of small GTPases and involvement of integrin/ligand signaling in extracellular release of HTLV-I virions between each three HTLV-I-infected T cell lines derived from HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients and from other origins as a control.

METHODS

Activity of small GTPases (Rho, Rac and Cdc42) was analyzed by pull-down assay with suppressive effect of both HTLV-I production and HTLV-I tax mRNA expression by anti-integrin-blocking antibodies.

RESULTS

All small GTPases were strongly activated in all cell lines derived from HAM/TSP patients, but not in control cell lines except one cell line. Treatment of all cell lines derived from HAM/TSP patients, but not all control cell lines, with anti-integrin-blocking antibodies significantly suppressed the level of HTLV-I p19 antigen in culture supernatants without downregulation of HTLV-I tax mRNA expression.

CONCLUSION

Significant involvement with integrin/ligand signaling in extracellular release of HTLV-I virions in cell lines derived from HAM/TSP patients suggests that HTLV-I-infected cells in HAM/TSP patients have the potential for the efficient spread of HTLV-I to uninfected cells.

摘要

目的

整合素/配体信号传导导致小GTP酶激活的活性可能通过病毒突触调节I型人类嗜T淋巴细胞病毒(HTLV-I)在细胞间传播的效率。我们比较了来自HTLV-I相关脊髓病/热带痉挛性截瘫(HAM/TSP)患者的三种HTLV-I感染的T细胞系与作为对照的其他来源的三种HTLV-I感染的T细胞系之间小GTP酶的活性以及整合素/配体信号传导在HTLV-I病毒粒子细胞外释放中的作用。

方法

通过下拉试验分析小GTP酶(Rho、Rac和Cdc42)的活性,并通过抗整合素阻断抗体对HTLV-I产生和HTLV-I tax mRNA表达的抑制作用进行分析。

结果

所有来自HAM/TSP患者的细胞系中的所有小GTP酶均被强烈激活,但除一个细胞系外,对照细胞系中未被激活。用抗整合素阻断抗体处理所有来自HAM/TSP患者的细胞系(但不是所有对照细胞系),可显著抑制培养上清液中HTLV-I p19抗原的水平,而不会下调HTLV-I tax mRNA的表达。

结论

整合素/配体信号传导在来自HAM/TSP患者的细胞系中HTLV-I病毒粒子的细胞外释放中起重要作用,这表明HAM/TSP患者中HTLV-I感染的细胞具有将HTLV-I有效传播至未感染细胞的潜力。

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