Nature of virally mediated changes in membrane permeability to small molecules.

1. The changes in membrane permeability to small molecules caused by Sendai virus [Pasternak & Micklem (1973) J. Membr. Biol. 14, 293-303] have been further characterized. The uptake of substances that are concentrated within cells is inhibited. Choline and 2-deoxyglucose, which become phosphorylated, and aminoisobutyrate and glycine, which are driven by a Na+-linked mechanism, are examples. The uptake of each compound under conditons where its diffusion across the plasma membrane is rate-limiting is stimulated by virus. Choline, 2-deoxyglucose and amino acids at high concentration, amino acids in Na+-free medium, and most substances at low temperature, are examples. It is concluded that virally mediated decrease of uptake is due to one of two causes. Substances that are accumulated by phosphorylation are not retained because of leakage of the phosphorylated metabolites out of cells. Substances that are accumulated by linkage to a Na+ gradient are no longer accumulated because of collapse of the gradient resulting from an increased permeability to Nat 2. Increased permeability to K+ and Na+ results in (a) membrane depolarization and (b) cell swelling. The latter event leads to haemolysis (for erythrocytes) and can lead to giant-cell (polykaryon) formation (for several cell types). 3. Recovery of cells can be temporarily achieved by the addition of Ca2+; permanent recovery requires incubation for some hours at 37 degrees C. 4. The possible significance of virally mediated permeability changes, with regard to clinical situations and to cell biology, is discussed.