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

The resistance of different mouse strains to MCMV infection strongly correlates with their ability to mount an effective NK cell response controlled by the Ly49H locus, positioned inside the NK gene complex (NKC) on mouse chromosome 6. Recently, it has been shown by two groups (Arase H. et al., Science 296:1323 and Smith H.R. et al., PNAS 99:8826) that the product of MCMV m157 gene serves as a ligand for an activating NK cell receptor, Ly49H. In this study we tested the significance of m157 gene product for NK cell-mediated virus control in vivo. MCMV m157 deletion mutant was generated and tested for its virulence and sensitivity to NK cells on both Ly49H positive and Ly49H negative mouse strains. The MCMV m157 deletion mutant reached a much higher titer compared to the wild type MCMV in C57BL/6 mice (Ly49H positive). Furthermore, the depletion of NK cells showed no effect on the virus titer in spleens of mice infected with the m157 deletion mutant virus. On the contrary, in BALB/c mice (Ly49H negative) the m157 deletion mutant reached a titer comparable to the wild type virus strain. From the above, it can be concluded that the product of MCMV m157 gene is playing a crucial role in NK cell-mediated control in LY49H positive mice.

MCMV; m157; NK cells; Ly49H

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