An earlier suggestion that guanidine may inhibit picornavirus replication by interfering with a monovalent cation-mediated event was tested by determining the effect of varying monovalent cation concentration in isotonic medium on the sensitivity of poliovirus replication in HeLa cells to 0.2 m-guanidine. Lowering [Na] in the medium to 50 m had no effect on virus replication. It was found that the degree of inhibition of virus replication by 0.2 m-guanidine was inversely related to [Na] in the medium: 99.8%, 99.1%, 38% and 0% inhibition in the presence of 50, 75, 100 and 145 m-Na respectively. Likewise, guanidine uptake by HeLa cells was also inversely related to [Na] in the medium. On the other hand, lowering medium [Na] to 50 or 75 m resulted in reduced intracellular [Na] and [K]. The increased sensitivity of virus replication to guanidine in the presence of low Na medium could be abolished with excess K in such medium. Excess K in low Na medium restored intracellular [Na] and reduced guanidine uptake. Thus, the increased sensitivity of poliovirus replication to guanidine in the presence of low Na medium correlated with reduced intracellular [Na] and [K] and elevated guanidine uptake.


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