Poliovirus infection interferes with the phorbol ester-induced differentiation of the monocytic U937 cell line.

Abstract

Monocytic U937 cells can differentiate in vitro into macrophage-like cells by treatment with phorbol esters such as phorbol 12-myristate 13-acetate (PMA). We have analyzed the effect of poliovirus infection in this pathway of differentiation. Poliovirus RNA replication took place in both untreated and PMA-treated U937 cells infected before or after PMA addition, although a slight reduction in poliovirus RNA levels was observed in PMA-treated cells at late times postinfection. Total protein synthesis remained unchanged during the first 5 h of infection both in normal and PMA-treated cells. However, an inhibition on total RNA synthesis was observed early in infection. PMA-induced c-myc mRNA expression was abolished when infection took place 1 h before PMA addition but was just partially inhibited when poliovirus was added 1 h after PMA stimulation. Fluorescence flow cytometry analysis revealed that poliovirus infection induced an increase in the number of 4F2 molecules per cell in normal U937 cells and a slight decrease in the number of positive cells for the antigens CD14, CD4 and CD11c in both untreated or PMA-treated U937 cells. These findings suggest that poliovirus infection of U937 cells interferes at various levels with monocyte maturation yielding cells which are unable to undergo the complete pathway of differentiation to macrophages.