Cytomegalovirus: sodium entry and development of cytomegaly in human fibroblasts.

A possible relationship between net Na+ entry and the development of CMV-induced cytomegaly (cell enlargement) was investigated in human fibroblasts derived from skin-muscle and thyroid tissue. We found that inhibiting cellular Na+ uptake, either by pharmacological means (amiloride, an inhibitor of Na+/H+ exchange) or by replacement of extracellular Na+ (by N-methyl-D-glucamine or choline), inhibited the development of cytomegaly. Furthermore, we noted a temporal parallelism between the development of cytomegaly and enhancement of ouabain-sensitive (O-S) 86Rb+ uptake. O-S 86Rb+ uptake is a monitor for the activity of the sodium pump resident in the plasmalemma of the fibroblasts. The enhanced O-S 86Rb+ uptake reflects either an increased intracellular Na+ concentration or an increased number of sodium pump complexes per fibroblast. Amiloride inhibited the enhancement of O-S 86Rb+ uptake, as well as cytomegaly development. Addition of amiloride at selected times after infection suggested that the same phase of virus replication was sensitive to the inhibitory effect of this drug on the enhancement of O-S 86Rb+ uptake and on the development of cytomegaly. There was also a similar pattern of inhibition of O-S 86Rb+ uptake and cytomegaly with increasing concentrations of amiloride. Thus, there may be a relationship between CMV-induced Na+ entry through activation of the Na+/H+ exchanger and development of cytomegaly.