We. Crowe et al., HUMAN CYTOMEGALOVIRUS-INFECTION ENHANCES OSMOTIC STIMULATION OF NA+ H+ EXCHANGE IN HUMAN FIBROBLASTS/, American journal of physiology. Cell physiology, 42(5), 1997, pp. 1739-1748
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.