Viral induction of AID is independent of the interferon and the Toll-like receptor signaling pathways but requires NF-kappaB.
Activation-induced cytidine deaminase (AID) is expressed in germinal centers of lymphoid organs during immunoglobulin diversification, in bone marrow B cells after infection with Abelson murine leukemia retrovirus (Ab-MLV), and in human B cells after infection by hepatitis C virus. To understand how viruses signal AID induction in the host we asked whether the AID response was abrogated in cells deficient in the interferon pathway or in signaling via the Toll-like receptors. Here we show that AID is not an interferon responsive gene and abrogation of Toll-like receptor signaling does not diminish the AID response. However, we found that NF-kappaB was required for expression of virally induced AID. Since NF-kappaB binds and activates the AID promoter, these results mechanistically link viral infection with AID transcription. Thus, induction of AID by viruses could be the result of several signaling pathways that culminate in NF-kappaB activation, underscoring the versatility of this host defense program.
Gourzi
Polyxeni
P
Laboratory of Lymphocyte Biology, The Rockefeller University, New York, NY 10021, USA.
Leonova
Tatyana
T
Papavasiliou
F Nina
FN
D000011:Abelson murine leukemia virus / Q000276:immunology*; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D003564:Cytidine Deaminase / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D009841:Oligonucleotides; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D051193:Toll-Like Receptors / Q000378:metabolism*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D016328:NF-kappa B; D009841:Oligonucleotides; D051193:Toll-Like Receptors; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase