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Intracellular cyclic adenosine monophosphate regulates the efficiency of intercellular transmission of human T‐lymphotropic virus type I
Author(s) -
Nakamura Tatsufumi,
Satoh Katsuya,
Nakamura Hideki,
Yamasaki Hironori
Publication year - 2014
Publication title -
clinical and experimental neuroimmunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.297
H-Index - 15
ISSN - 1759-1961
DOI - 10.1111/cen3.12097
Subject(s) - intracellular , adenosine , phosphoprotein , microbiology and biotechnology , forskolin , cyclic adenosine monophosphate , adenylyl cyclase , tropical spastic paraparesis , cell culture , biology , chemistry , phosphorylation , biochemistry , enzyme , receptor , myelopathy , genetics , neuroscience , spinal cord
Objective To 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. Methods HCT‐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/K30 luc reporter cells, the relative luc activities were calculated to analyze the efficiency of intercellular transmission of HTLV‐I. The intracellular levels of cyclic adenosine monophosphate (c AMP ) or cyclic guanosine monophosphate (c GMP ) were measured in enzyme‐linked immunoassays. The expression of phosphorylated vasodilator‐stimulated phosphoprotein (p‐VASP) was analyzed by western blotting. Results Treatment 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 c AMP concentration. Furthermore, the relative luc activity was significantly decreased. The intracellular c AMP , but not c GMP 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. Conclusions The intracellular c AMP 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 c AMP levels.