Human cytomegalovirus infection enhances osmotic stimulation of Na+/H+ exchange in human fibroblasts.
Infection with human cytomegalovirus (HCMV) causes an enlargement (cytomegaly) of human fibroblasts (MRC-5). As a first step toward determining whether solute uptake, mediated in part by Na+/H+ exchange, is responsible for the development of cytomegaly, we studied the effects of HCMV infection on intracellular pH (pHi) regulation (nominal CO2/ HCO3- 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 pHi is 0.1-0.2 pH unit more alkaline; the intrinsic buffering power of the cytoplasm was reduced by approximately 40-50%; acid-loading H(+)-equivalent fluxes were reduced; and there were alterations of Na+/H+ exchanger (NHE) properties, including an alkaline shift of the pHi dependence of activity, a reduction of the apparent affinity for extracellular Na+, and an increase of the apparent maximum velocity and a large increase in stimulation by a hyperosmotic challenge. These results indicate that HCMV infection exerts a profound effect on functional properties of the NHE, on acid-loading mechanisms, and on intrinsic cellular buffering power. These effects are consistent with a role for the NHE in the development of cytomegaly.
Crowe
W E
WE
Department of Physiology, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania 19129, USA.
Altamirano
A A
AA
Russell
J M
JM
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D002472:Cell Transformation, Viral; D003587:Cytomegalovirus / Q000502:physiology*; D005347:Fibroblasts; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006982:Hypertonic Solutions; D007700:Kinetics; D008168:Lung; D009550:Nigericin / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*
D006982:Hypertonic Solutions; D017923:Sodium-Hydrogen Exchangers; C067984:5-diethylamiloride; D000584:Amiloride; D012964:Sodium; D009550:Nigericin