title: An identical miRNA of the human JC and BK polyoma viruses targets the stress-induced ligand ULBP3 to escape immune elimination.
abstract: The human polyoma viruses JCV and BKV establish asymptomatic persistent infection in 65%-90% of humans but can cause severe illness under immunosuppressive conditions. The mechanisms by which these viruses evade immune recognition are unknown. Here we show that a viral miRNA identical in sequence between JCV and BKV targets the stress-induced ligand ULBP3, which is a protein recognized by the killer receptor NKG2D. Consequently, viral miRNA-mediated ULBP3 downregulation results in reduced NKG2D-mediated killing of virus-infected cells by natural killer (NK) cells. Importantly, when the activity of the viral miRNA was inhibited during infection, NK cells killed the infected cells more efficiently. Because NKG2D is also expressed by various T cell subsets, we propose that JCV and BKV use an identical miRNA that targets ULBP3 to escape detection by both the innate and adaptive immune systems, explaining how these viruses remain latent without being eliminated by the immune system.
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada, Faculty of Medicine, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Bauman
authors.forename: Daphna
authors.initials: D
authors.lastname: Nachmani
authors.forename: Alon
authors.initials: A
authors.lastname: Vitenshtein
authors.forename: Pinchas
authors.initials: P
authors.lastname: Tsukerman
authors.forename: Nir
authors.initials: N
authors.lastname: Drayman
authors.forename: Noam
authors.initials: N
authors.lastname: Stern-Ginossar
authors.forename: Dikla
authors.initials: D
authors.lastname: Lankry
authors.forename: Raizy
authors.initials: R
authors.lastname: Gruda
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
mesh_terms: D001739:BK Virus / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D045744:Cell Line, Tumor; D015536:Down-Regulation; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D057131:Immune Evasion; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000276:immunology; D007577:JC Virus / Q000235:genetics* / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D035683:MicroRNAs / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000276:immunology; D027601:Polyomavirus Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D012367:RNA, Viral / Q000235:genetics / Q000276:immunology*
chemical_list: D058851:GPI-Linked Proteins; D036341:Intercellular Signaling Peptides and Proteins; C527085:KLRK1 protein, human; D035683:MicroRNAs; D055655:NK Cell Lectin-Like Receptor Subfamily K; D012367:RNA, Viral; C423229:ULBP3 protein, human