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 repertoi re 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 lar ge virus-specific gene Families located at either flanking region of the 23 5 kb MCMV genome. The MHC I subversive genes belong to the early class of g enes and code for type I transmembrane glycoproteins. The ml52-encoded 37/4 0 kDa glycoprotein interacts with MHC I transiently and retains class I com plexes 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 ER. D ue to sorting signals in its cytoplasmic tail, gp48 redirects MHC I to endo lysosomal compartments for proteolytic destruction. Likewise, the 34 kDa gl ycoprotein 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-d ependent attenuation of a m152 deletion mutant virus proves for the first t ime that inhibition of antigen presentation is indeed essential for the bio logical fitness of CMVs in vivo.