Fukushima Naomi, Nakamura Tatsufumi, Nishiura Yoshihiro, Ida Hiroaki, Aramaki Toshiyuki, Eguchi Katsumi
Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Intervirology. 2008;51(2):123-9. doi: 10.1159/000139130. Epub 2008 Jun 16.
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.
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.
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.
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.
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。
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。
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。
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。