Murine cytomegalovirus m157 mutation and variation leads to immune evasion of natural killer cells.
Effective natural killer (NK) cell recognition of murine cytomegalovirus (MCMV)-infected cells depends on binding of the Ly49H NK cell activation receptor to the m157 viral glycoprotein. Here we addressed the immunological consequences of variation in m157 sequence and function. We found that most strains of MCMV possess forms of m157 that evade Ly49H-dependent NK cell activation. Importantly, repeated passage of MCMV through resistant Ly49H+ mice resulted in the rapid emergence of m157 mutants that elude Ly49H-dependent NK cell responses. These data provide the first molecular evidence that NK cells can exert sufficient immunological pressure on a DNA virus, such that it undergoes rapid and specific mutation in an NK cell ligand enabling it to evade efficient NK cell surveillance.
Immunology and Virology Program, Centre for Opthalmology and Visual Science, University of Western Australia, Nedlands, WA 6009, Australia.
Valentina
V
Voigt
Catherine A
CA
Forbes
Joanne N
JN
Tonkin
Mariapia A
MA
Degli-Esposti
Hamish R C
HR
Smith
Wayne M
WM
Yokoyama
Anthony A
AA
Scalzo
D000818:Animals; D000950:Antigens, Ly / Q000235:genetics; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004247:DNA / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D014644:Genetic Variation; D006023:Glycoproteins / Q000737:chemistry; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D008024:Ligands; D016131:Lymphocyte Subsets; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D018146:Muromegalovirus / Q000235:genetics*; D009154:Mutation; D055650:NK Cell Lectin-Like Receptor Subfamily A; D016133:Polymerase Chain Reaction; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like; D013154:Spleen / Q000821:virology; D014162:Transfection; D001616:beta-Galactosidase / Q000378:metabolism
D000950:Antigens, Ly; D006023:Glycoproteins; C527096:Klra8 protein, mouse; D037181:Lectins, C-Type; D008024:Ligands; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like; D004247:DNA; D001616:beta-Galactosidase