Intracellular cyclic adenosine monophosphate regulates the efficiency of intercellular transmission of human T-lymphotropic virus type I.
Intracellular cyclic adenosine monophosphate regulates the efficiency of intercellular transmission of human T-lymphotropic virus type I.
复制标题
细胞内环磷酸腺苷调节 I 型人类 T 淋巴细胞病毒的细胞间传播效率。
DOI：
10.1111/cen3.12097
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Yamasaki H.
中科院分区：
文献类型：
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作者：
Nakamura T;Satoh K;Nakamura H;Yamasaki H.
目的通过对HTLV‐1相关脊髓病/热带痉挛性截瘫（HAM/TSP）患者和HTLV‐1携带者感染的T细胞株进行比较研究，探讨HTLV‐1型人嗜T淋巴病毒（HTLV‐1）的细胞间传播效率与细胞骨架重组过程中肌动蛋白聚合信号的关系。方法分别从HAM/TSP患者和HTLV‐1携带者身上提取shct‐5和TL‐Su细胞作为HTLV‐1感染的T细胞系。将HTLV‐1感染的T细胞系与H9/K30lucreporter细胞共培养后，计算其相对luc活性，分析HTLV‐1的细胞间传播效率。用酶联免疫法测定细胞内环磷酸腺苷（cAMP）或环鸟苷（cGMP）水平。western blotting分析磷酸化血管扩张剂刺激磷酸化蛋白（p - VASP）的表达。结果用肌动蛋白聚合抑制剂latrunculin B处理HCT - 5细胞可显著抑制其相对luc活性。用腺苷酸环化酶激活剂forskolin处理的HCT‐5细胞的Western blotting分析显示p‐VASP上调，同时细胞内cAMP浓度显著增加。相对luc活性显著降低。HCT‐5的细胞内cAMP水平明显低于TL‐Su，但cGMP水平不明显。血管扩张剂刺激的磷酸化蛋白在HCT‐5中比在TL‐Su中磷酸化更少。相对luc活性在HCT‐5中显著高于在TL‐Su中。结论在p - VASP表达的控制下，细胞内cAMP浓度可调节HTLV - I细胞间传递效率，提示HTLV - I感染的HAM/TSP患者细胞内cAMP水平下调可增强HTLV - I细胞间传递潜能。
ObjectiveTo investigate the relationship between the intercellular transmission efficiency of human T‐lymphotropic virus type I (HTLV‐I) and the signaling involved in actin polymerization during cytoskeletal reorganization in a comparative study of HTLV‐I‐infected T‐cell lines derived from an HTLV‐I‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) patient or an HTLV‐I carrier.MethodsHCT‐5 and TL‐Su cells derived from an HAM/TSP patient and an HTLV‐I carrier, respectively, were used as HTLV‐I‐infected T‐cell lines. After co‐cultivation of each HTLV‐I‐infected T‐cell line with H9/K30lucreporter cells, the relative luc activities were calculated to analyze the efficiency of intercellular transmission of HTLV‐I. The intracellular levels of cyclic adenosine monophosphate (cAMP) or cyclic guanosine monophosphate (cGMP) were measured in enzyme‐linked immunoassays. The expression of phosphorylated vasodilator‐stimulated phosphoprotein (p‐VASP) was analyzed by western blotting.ResultsTreatment of HCT‐5 cells with latrunculin B, an inhibitor of actin polymerization, significantly suppressed the relative luc activity. Western blotting analysis of HCT‐5 cells treated with the adenylyl cyclase activator forskolin showed upregulation of p‐VASP, with a concomitant and significant increase in the intracellular cAMP concentration. Furthermore, the relative luc activity was significantly decreased. The intracellular cAMP, but not cGMP levels, were significantly lower in HCT‐5 than in TL‐Su. Vasodilator‐stimulated phosphoprotein appeared less phosphorylated in HCT‐5 than in TL‐Su. The relative luc activity was significantly higher in HCT‐5 than in TL‐Su.ConclusionsThe intracellular cAMP concentration regulates the efficiency of intercellular HTLV‐I transmission under the control of p‐VASP expression, suggesting the intercellular transmission potential of HTLV‐I‐infected T cells of HAM/TSP patients is enhanced by downregulated intracellular cAMP levels.