Hengel H, Reusch U, Gutermann A, Ziegler H, Jonjic S, Lucin P, Koszinowski U H
Max von Pettenkofer-Institut, Ludwig-Maximilians-Universität München, Germany.
Immunol Rev. 1999 Apr;168:167-76. doi: 10.1111/j.1600-065x.1999.tb01291.x.
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.
巨细胞病毒（CMV）是疱疹病毒β亚群的典型病毒。鼠巨细胞病毒（MCMV）以小鼠作为其自然宿主。在病毒中，CMV进化出了最广泛的基因库来破坏MHC I类分子的功能。迄今为止，已鉴定出三种影响MHC I复合物的MCMV蛋白。它们由位于235 kb MCMV基因组侧翼区域的大型病毒特异性基因家族的成员编码。MHC I破坏基因属于早期基因类别，编码I型跨膜糖蛋白。m152编码的37/40 kDa糖蛋白与MHC I短暂相互作用，并在其前往内溶酶体的过程中将I类复合物保留在内质网（ER）-高尔基体中间区室中。相比之下，m06编码的48 kDa糖蛋白在FR中与三元MHC I类分子紧密结合。由于其细胞质尾巴中的分选信号，gp48将MHC I重定向至内溶酶体区室进行蛋白水解破坏。同样，m04编码的34 kDa糖蛋白在ER中与MHC I类复合物紧密结合，但gp34/MHC I复合物到达质膜。m152缺失突变病毒的CD8 + T细胞依赖性减毒首次证明，抑制抗原呈递对于CMV在体内的生物学适应性确实至关重要。
