Intracellular cyclic adenosine monophosphate regulates the efficiency of intercellular transmission of human T-lymphotropic virus type I

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Abstract

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 (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.

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 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.

Conclusions

The 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.

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