Obligatory role of Ca²⁺ in the cytotoxic activity of dengue virus-induced cytotoxin

Abstract

The role of calcium ions (Ca²⁺) in the cytotoxic activity of the dengue type 2 virus (DV)-induced macrophage (Mφ) cytotoxin (CF₂) was investigated in the present study. The findings show that CF₂ prepared in Ca²⁺-free medium had no cytotoxic activity on normal mouse spleen cells suspended in Ca²⁺-free medium but killed the cells suspended in the medium with Ca²⁺. Substitution with calcium chloride restored the cytotoxic activity of CF₂ the optimal dose being Io^-4M concentration. CF₂ induced an influx of Ca²⁺, as assayed by uptake of radiolabelled calcium chloride (⁴⁵Ca), in the susceptible target cells, viz. Mφ and T lymphocytes. The cytotoxic activity of CF₂ as well as the CF₂-induced influx of ⁴⁵Ca was inhibited by treatment of the target cell with the calcium channel blocking drugs verapamil and nifedipine. Thus, the presence of Ca²⁺ is obligatory for the cytotoxic activity of CF₂ and cell death is associated with increased intracellular Ca²⁺.