HUMAN CYTOMEGALOVIRUS-INFECTION ENHANCES OSMOTIC STIMULATION OF NA+ H+ EXCHANGE IN HUMAN FIBROBLASTS/

Infection with human cytomegalovirus (HCMV) causes an enlargement (cyt omegaly) of human fibroblasts (MRC-5). As a first step toward determin ing whether solute uptake, mediated in part by Na+/H+ exchange, is res ponsible for the development of cytomegaly, we studied the effects of HCMV infection on intracellular pH (pH(i)) regulation (nominal CO2/HCO 3- concn = 0) by comparing cytomegalic cells with mock-infected cells. Seventy-two hours after HCMV infection of MRC-5 cells we observed the following changes relative to mock-infected cells: resting pH(i) is 0 .1-0.2 pH unit more alkaline; the intrinsic buffering power of the cyt oplasm was reduced by similar to 40-50%; acid-loading H+-equivalent fl uxes were reduced; and there were alterations of Na+/H+ exchanger (NHE ) properties, including an alkaline shift of the pH(i) dependence of a ctivity, a reduction of the apparent affinity for extracellular Na+, a nd an increase of the apparent maximum velocity and a large increase i n stimulation by a hyperosmotic challenge. These results indicate that HCMV infection exerts a profound effect on functional properties of t he NHE, on acid-loading mechanisms, and on intrinsic cellular bufferin g power. These effects are consistent with a role for the NHE in the d evelopment of cytomegaly.