Cytomegaloviral Control of MHC Class I Function in the Mouse

Cytomegaloviruses (CMVs) represent prototypic viruses of the beta-subgroup of herpesviruses. Murine cytomegalovirus (MCMV) infects mice as its natural host. Among viruses, CMVs have evolved the most extensive genetic repertoire to subvert MHC class I functions. To date three MCMV proteins have been identified which affect MHC I complexes. They are encoded by members of large virus-specific gene families located at either flanking region of the 235 kb MCMV genome. The MHC I subversive genes belong to the early class of genes and code for type I transmembrane glycoproteins. The m152-encoded 37/40 kDa glycoprotein interacts with MHC I transiently and retains class I complexes in the endoplasmic reticulum (ER) Golgi intermediate compartment on its journey to the endolysosome. In contrast, the m06-encoded glycoprotein of 48 kDa complexes tightly with ternary MHC class I molecules in the FR. Due to sorting signals in its cytoplasmic tail, gp48 redirects MHC I to endolysosomal compartments for proteolytic destruction. Likewise, the 34 kDa glycoprotein encoded by m04 binds tightly to MHC class I complexes in the ER but the gp34/MHC I complex reaches the plasma membrane. The CD8+ T-cell-dependent attenuation of a m152 deletion mutant virus proves for the first time that inhibition of antigen presentation is indeed essential for the biological fitness of CMVs in vivo.