Human cytomegalovirus strain-dependent changes in NK cell recognition of infected fibroblasts

NK cells play a key role in the control of CMV infection in mice, but the m echanism by which NK cells can recognize and kill CMV-infected cells is unc lear. In this study, the modulation of NK cell susceptibility of human CMV (hCMV)-infected cells was examined. We used a human lung and a human foresk in fibroblast cell line infected with clinical isolates (4636, 13B, or 109B ) or with laboratory strains (AD169, Towne). The results indicate that all three hCMV clinical isolates confer a strong NK resistance, whereas only ma rginal or variable effects in the NK recognition were found when the labora tory strains were used. The same results were obtained regardless of the co nditions of infection, effector cell activation status, cell culture condit ions, and/or donor-target cell combinations. The NK cell inhibition did not correlate with HLA class I expression levels on the surface of the target cell and was independent of the leukocyte Ig-like receptor-1, as evaluated in Ab blocking experiments. No relevant changes were detected in the adhesi on molecules ICAM-I and LFA-3 expressed on the cell surface of cells infect ed with hCMV clinical and laboratory strains. We conclude that hCMV possess es other mechanisms, related neither to target cell, expression of HLA-I or adhesion molecules nor to NK cell expression of leukocyte Ig-like receptor -1, that confer resistance to NK cell recognition, Such mechanisms may be l ost during in vitro passage of the virus. These results emphasize the diffe rences between clinical hCMV isolates compared with laboratory strains.