Requirement for endocytosis of poly(rI).poly(rC) to generate toxicity on interferon-treated LM cells.

Poly(rI).poly(rC) induces a lytic reaction in interferon-treated mouse LM cells. We have attempted to determine whether the intracellular penetration of poly(rI).poly(rC) is a prerequisite for cell lysis and to gain some insight into the pathway followed. We found that poly(rI).poly(rC) coupled to Sepharose beads was unable to generate lysis of interferon-treated cells whereas the cells underwent lysis after microinjection of poly(rI).poly(rC). Some inhibitors of endocytosis were found to inhibit the development of the lytic reaction. Lysosomotropic amines or a low temperature (19 degrees C) blocked endocytosis of poly(rI).poly(rC) but did not prevent its uptake. The internalization of poly(rI).poly(rC) was energy-dependent and was blocked when sodium azide and 2-deoxyglucose were added simultaneously. We conclude that poly(rI).poly(rC) is internalized and reaches an acidic compartment before triggering the lytic reaction in the cell.