Major histocompatibility complex class I allele-specific cooperative and competitive interactions between immune evasion proteins of cytomegalovirus

被引:145
作者
Wagner, M
Gutermann, A
Podlech, J
Reddehase, MJ
Koszinowski, UH
机构
[1] Univ Munich, Max Von Pettenkofer Inst, Dept Virol, D-80336 Munich, Germany
[2] Johannes Gutenberg Univ Mainz, Inst Virol, D-55101 Mainz, Germany
关键词
murine cytomegalovirus; BAC; immune evasion; MHC class II; allele;
D O I
10.1084/jem.20020811
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Cytomegaloviruses (CMVs) deploy a set of genes for interference with antigen presentation in the major histocompatibility complex (MHC) class I pathway. In murine CMV (MCMV), three genes were identified so far: m04/gp34, m06/gp48, and m152/gp40. While their function as immunoevasins was originally defined after their selective expression, this may not necessarily reflect their biological role during infection. The three immunoevasins might act synergistically, but they might also compete for their common substrate, the MHC class I complexes. To approach this question in a systematic manner, we have generated a complete set of mutant viruses v,,with deletions of the three genes in all seven possible combinations. Surface expression of a set of MHC class I molecules specified by haplotypes H-2(d) (K-d, D-d, and L-d) and H-2(b) (K-b and D-b) was the parameter for evaluation of the interference with class I trafficking. The data show the following: first, there exists no additional MCMV gene of major influence on MHC class I surface expression; second, the strength of the inhibitory effect of immunoevasins shows an allele-specific hierarchy; and third, the immunoevasins act not only synergistically but can, in certain combinations, interact antagonistically. In essence, this work highlights the importance of studying the immunosubversive mechanisms of cytomegaloviruses in the context of gene expression during the viral replicative cycle in infected cells.
引用
收藏
页码:805 / 816
页数:12
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