engleski

The MCMV m152/gp40 glycoprotein achieves simulateous avoidance of CD8+ and NK cell-mediated immune control

The MCMV glycoprotein gp40, encoded by the m152 gene retains MHC class-I complexes in the ERGIC/cis-Golgi compartment, allowing the virus to evade control by CD8 positive T lymphocytes in vivo. Since cell surface class-I molecules interact with inhibitory receptors to avoid NK cell attack, down-modulation of MHC-I molecules may increase MCMV susceptibility to NK cells. However, we found that gp40 severely inhibits NK cell-mediated virus control in vivo. This effect is mouse strain dependent but independent of Cmv1, a locus which restricts early MCMV replication in the spleen through the action of NK cells. In mouse strains sensitive to the gp40-medaited effect (e.g. BALB/c) the NK cell response is strongly attenuated by the expression of m152, while in resistant strains (e.g. B6) replication of both, the m152 deletion mutant and the m152 revertant virus is efficiently controlled by NK cells. Transfer studies of MCMV infected cells from resistant into sensitive strains reviled that both NK receptors as well as ligands present on NK stimulator cells determine the m152/gp40 phenotype. Taking advantage of intra-natural killer complex (NKC) recombinant BALB/c/B6 and congenic mouse strains we are currently mapping loci encompassing gp40-sensitive NK cell receptor(s) on mouse chromosome 6.

MCMV; NK cells; m152; immunevasion

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