Mechanism of the Antiviral Activity Resulting from Sequential Administration of Complementary Homopolyribonucleotides to Cell Cultures

The antiviral activity of the double-stranded complex poly(rI) . poly(rC) in cell culture was restored or even surpassed if the constituent homopolymers were administered separately. Poly(rI) primed the cells for the antiviral activity of poly(rC) and poly(rC) primed for poly(rI), but neither poly(rI) nor poly(rC) primed the cells for the antiviral activity of noncomplementary homopolynucleotides. The priming effect of poly(rI) was significantly reduced if the poly(rI)-primed cells were treated with either T(1) ribonuclease or diethylaminoethyl (DEAE)-dextran before addition of poly(rC), and the priming effect of poly(rC) was significantly reduced if the poly(rC)-primed cells were treated with either pancreatic ribonuclease or DEAE-dextran before addition of poly(rI). (3)H-labeled poly(rC) bound more rapidly to poly(rI)-treated cells than to control cells. Cell-associated poly(rC) was markedly more resistant to pancreatic ribonuclease treatment if the cells had been incubated with poly(rI) before exposure to poly(rC). Our results clearly indicate that poly(rI) and poly(rC) added successively to cell cultures do not act independently but reunite at the cellular level, most likely at the outer cell membrane.