title: The antiviral factor APOBEC3G enhances the recognition of HIV-infected primary T cells by natural killer cells.
abstract: APOBEC3G (A3G) is an intrinsic antiviral factor that inhibits the replication of human immunodeficiency virus (HIV) by deaminating cytidine residues to uridine. This causes guanosine-to-adenosine hypermutation in the opposite strand and results in inactivation of the virus. HIV counteracts A3G through the activity of viral infectivity factor (Vif), which promotes degradation of A3G. We report that viral protein R (Vpr), which interacts with a uracil glycosylase, also counteracted A3G by diminishing the incorporation of uridine. However, this process resulted in activation of the DNA-damage-response pathway and the expression of natural killer (NK) cell-activating ligands. Our results show that pathogen-induced deamination of cytidine and the DNA-damage response to virus-mediated repair of the incorporation of uridine enhance the recognition of HIV-infected cells by NK cells.
authors.affiliation: Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Norman
authors.forename: Michael
authors.initials: M
authors.lastname: Mashiba
authors.forename: Lucy A
authors.initials: LA
authors.lastname: McNamara
authors.forename: Adewunmi
authors.initials: A
authors.lastname: Onafuwa-Nuga
authors.forename: Estelle
authors.initials: E
authors.lastname: Chiari-Fort
authors.forename: Wenwen
authors.initials: W
authors.lastname: Shen
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Collins
mesh_terms: D000071480:APOBEC-3G Deaminase; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000502:physiology*; D003602:Cytotoxicity, Immunologic; D004249:DNA Damage; D016336:Gene Products, vpr / Q000502:physiology; D006678:HIV / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism; D013601:T-Lymphocytes / Q000821:virology*; D014529:Uridine / Q000378:metabolism
chemical_list: D016336:Gene Products, vpr; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase; D014529:Uridine