engleski

Selective down-regulation of the NKG2D ligand H60 by mouse cytomegalovirus m155 glycoprotein

Both human and mouse cytomegalovirus (CMV) encode proteins that inhibit the activation of NK cells by down-regulating cellular ligands for the activating NK cell receptor, NKG2D. Up to now three ligands for the NKG2D receptor have been identified in mice: RAE-1, H60 and MULT-1. Resistance of mouse strains to murine CMV (MCMV) infection is determined by their ability to generate an effective NK cell response. The MCMV gene m152, a member of the m145 gene family, down-regulates expression of RAE-1 in order to avoid NK cell control in vivo. Here we report that the m155 gene, another member of the m145 gene family, encodes a protein that interferes with the expression of H60 on the surface of infected cells. The deletion of the m155 gene leads to restoration of H60 expression on the cell surface and NK cell-dependent attenuation of the mutant virus in vivo. The acquisition of Endo H resistance and the preserved half-life of H60 in MCMV-infected cells indicate that the m155-mediated effect must take place in a compartment after H60 exits from the ERGIC/cis-Golgi.

m155; NK CELLS; NKG2D; IMMUNOEVASION

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