title: Major histocompatibility complex class I allele-specific cooperative and competitive interactions between immune evasion proteins of cytomegalovirus.
abstract: 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 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.
authors.affiliation: Max von Pettenkofer Institute, Department for Virology, Ludwig-Maximilians-Universität München, 80336 Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Wagner
authors.forename: Anja
authors.initials: A
authors.lastname: Gutermann
authors.forename: Jürgen
authors.initials: J
authors.lastname: Podlech
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Reddehase
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: Koszinowski
mesh_terms: D000483:Alleles; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D004926:Escherichia coli / Q000235:genetics; D005347:Fibroblasts / Q000821:virology; D005805:Genes, MHC Class I; D006023:Glycoproteins / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018146:Muromegalovirus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D016133:Polymerase Chain Reaction; D014764:Viral Proteins; D014779:Virus Replication
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D014764:Viral Proteins; C104832:gp34 protein, cytomegalovirus; C104783:m152 protein, cytomegalovirus