HUMAN CYTOMEGALOVIRUS-INFECTION STIMULATES CL- HCO3- EXCHANGER ACTIVITY IN HUMAN FIBROBLASTS/

The effects of human cytomegalovirus (HCMV) infection on Cl-/HCO3- exc hanger activity in human lung fibroblasts (MRC-5 cells) were studied u sing fluorescent, ion-sensitive dyes. The intracellular pH (pH(i)) of mock- and HCMV-infected cells bathed in a solution containing 5% CO2-2 5 mM HCO3- were nearly the same. However, replacement of external Cl- with gluconate caused an H2DIDS-inhibitable (100 mu M) increase in the pH(i) of HCMV-infected cells but not in mock-infected cells. Continuo us exposure to hyperosmotic external media containing CO2/HCO3- caused the pH(i) of both cell types to increase. The pH(i) remained elevated in mock-infected cells. However, in HCMV-infected cells, the pH(i) pe aked and then recovered toward control values. This pH(i) recovery pha se was completely blocked by 100 mu M H2DIDS. In the presence of CO2/H CO3-, there was an H2DIDS-sensitive component of net Cl- efflux (exter nal Cl- was substituted with gluconate) that was less in mock- than in HCMV-infected cells. When nitrate was substituted for external Cl- (i n the nominal absence of CO2/HCO3-), the H2DIDS-sensitive net Cl- effl ux was much greater from HCMV- than from mock-infected cells. In mock- infected cells, H2DIDS-sensitive, net Cl- efflux decreased as pH(i) in creased, whereas for HCMV-infected cells, efflux increased as pH(i) in creased. All these results are consistent with an HCMV-induced enhance ment of Cl-/HCO3- exchanger activity.