engleski

The significance of MCMV m157 gene product in NK cell-mediated control of MCMV infection in vivo

Aim of the study: The aim of this study was to determine the function of MCMV m157 gene product in vivo. Materials and Methods: The m157 deletion mutant and its revertant virus strain were tested on both MCMV sensitive and MCMV resistant mouse strains. Mice were depleted of NK cells or left undepleted one day before i.v. injection of viruses. Virus titers in different organs were determined three days after infection by standard plaque forming assay on mouse embryonic fibroblasts. Results: Based on their susceptibility to MCMV infection, conventional laboratory mouse strains could be divided into two groups: MCMV susceptible mouse strains, represented by BALB/c mice, and MCMV resistant mouse strains, represented by C57BL/6 mice. The resistance strongly correlates with the ability of mouse strains to mount an effective NK cell response, which is controlled by the Ly49H locus, positioned inside the NK gene complex on mouse chromosome 6. Recently, it has been shown by two independent groups (Smith H.R. et al., PNAS 99(13): 8826-31, Arase H. et al., Science 296(5571): 1323-6) that MCMV m157 gene encodes the ligand for an activating NK cell receptor, Ly49H, and that the same product can also serve as a ligand for an inhibitory NK cell receptor, possibly Ly49 I. Here we confirm that the MCMV m157 gene product plays a role in vivo as well. The m157 deletion mutant reached a much higher titer when compared to m157 revertant virus strain in C57BL/6 mice. Depletion of NK cells showed no effect on virus titer in spleen of mice infected with m157 deletion mutant virus, whereas at the same time, revertant and w.t. virus strains showed equal susceptibility to NK cell control. These findings, however, could not be fully applied to all organs, indicating that different NK-cell mediated control mechanisms of MCMV infection could be involved in different tissues. Conclusion: The product of MCMV m157 gene plays a crucial role for NK cell-mediated control as a ligand for Ly49H NK cell receptor in LY49H positive mouse strains. At the same time, in Ly49H negative mice, it appears that the product of this gene could serve as a ligand for inhibitory NK cell receptors in vivo.

MCMV; m157; NK cells; Ly49H

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