Farrell H E, Vally H, Lynch D M, Fleming P, Shellam G R, Scalzo A A, Davis-Poynter N J
Department of Microbiology, University of Western Australia, Nedlands.
Nature. 1997 Apr 3;386(6624):510-4. doi: 10.1038/386510a0.
Herpesviruses, such as murine and human cytomegalovirus (MCMV and HCMV), can establish a persistent infection within the host and have diverse mechanisms as protection from host immune defences. Several herpesvirus genes that are homologous to host immune modulators have been identified, and are implicated in viral evasion of the host immune response. The discovery of a viral major histocompatibility complex (MHC) class I homologue, encoded by HCMV, led to speculation that it might function as an immune modulator and disrupt presentation of peptides by MHC class I to cytotoxic T cells. However, there is no evidence concerning the biological significance of this gene during viral infection. Recent analysis of the MCMV genome has also demonstrated the presence of a MHC class I homologue. Here we show that a recombinant MCMV, in which the gene encoding the class I homologue has been disrupted, has severely restricted replication during the acute stage of infection compared with wild-type MCMV. We demonstrate by in vivo depletion studies that natural killer (NK) cells are responsible for the attenuated phenotype of the mutant. Thus the viral MHC class I homologue contributes to immune evasion through interference with NK cell-mediated clearance.
疱疹病毒，如鼠巨细胞病毒和人巨细胞病毒（MCMV和HCMV），可在宿主体内建立持续感染，并有多种机制来抵御宿主的免疫防御。已鉴定出几种与宿主免疫调节剂同源的疱疹病毒基因，它们与病毒逃避宿主免疫反应有关。由HCMV编码的病毒主要组织相容性复合体（MHC）I类同源物的发现，引发了人们的猜测，即它可能作为一种免疫调节剂发挥作用，并干扰MHC I类向细胞毒性T细胞呈递肽段。然而，尚无证据表明该基因在病毒感染过程中的生物学意义。对MCMV基因组的最新分析也证实了MHC I类同源物的存在。在此我们表明，与野生型MCMV相比，编码I类同源物的基因已被破坏的重组MCMV在感染急性期的复制受到严重限制。我们通过体内耗竭研究证明，自然杀伤（NK）细胞是突变体减毒表型的原因。因此，病毒MHC I类同源物通过干扰NK细胞介导的清除作用来促进免疫逃逸。
