A role for activation-induced cytidine deaminase in the host response against a transforming retrovirus.
Activation-induced cytidine deaminase (AID) is specifically expressed in the germinal centers of lymphoid organs, where it initiates targeted hypermutation of variable regions of immunoglobulin genes in response to stimulation by antigen. Ectopic expression of AID, however, mediates generalized hypermutation in eukaryotes and prokaryotes. Here, we present evidence that AID is induced outside the germinal center in response to infection by the Abelson murine leukemia virus. The genotoxic activity of virally induced AID resulted in checkpoint kinase-1 (chk1) phosphorylation and ultimately restricted the proliferation of the infected cell. At the same time, it induced NKG2D ligand upregulation, which alerts the immune system to the presence of virally transformed cells. Hence, in addition to its known function in immunoglobulin diversification, AID is active in innate defense against a transforming retrovirus.
Gourzi
Polyxeni
P
Laboratory of Lymphocyte Biology, Rockefeller University, 1230 York Avenue, New York, New York 10021.
Leonova
Tatyana
T
Laboratory of Lymphocyte Biology, Rockefeller University, 1230 York Avenue, New York, New York 10021.
Papavasiliou
F Nina
FN
Laboratory of Lymphocyte Biology, Rockefeller University, 1230 York Avenue, New York, New York 10021. Electronic address: papavasiliou@rockefeller.edu.
D000011:Abelson murine leukemia virus / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology; D001853:Bone Marrow / Q000201:enzymology / Q000821:virology; D000071877:Checkpoint Kinase 1; D003564:Cytidine Deaminase / Q000235:genetics / Q000502:physiology*; D003643:Death; D007942:Leukemia, Experimental / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D008024:Ligands; D051379:Mice; D008815:Mice, Inbred Strains; D055655:NK Cell Lectin-Like Receptor Subfamily K; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D012192:Retroviridae Infections / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D014412:Tumor Virus Infections / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
C527086:Klrk1 protein, mouse; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1; C000605869:Chek1 protein, mouse; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase