Host immune system gene targeting by a viral miRNA.
Virally encoded microRNAs (miRNAs) have recently been discovered in herpesviruses. However, their biological roles are mostly unknown. We developed an algorithm for the prediction of miRNA targets and applied it to human cytomegalovirus miRNAs, resulting in the identification of the major histocompatibility complex class I-related chain B (MICB) gene as a top candidate target of hcmv-miR-UL112. MICB is a stress-induced ligand of the natural killer (NK) cell activating receptor NKG2D and is critical for the NK cell killing of virus-infected cells and tumor cells. We show that hcmv-miR-UL112 specifically down-regulates MICB expression during viral infection, leading to decreased binding of NKG2D and reduced killing by NK cells. Our results reveal a miRNA-based immunoevasion mechanism that appears to be exploited by human cytomegalovirus.
Stern-Ginossar
Noam
N
Lautenberg Center for General and Tumor Immunology, Hebrew University Hadassah Medical School, Jerusalem, Israel.
Elefant
Naama
N
Zimmermann
Albert
A
Wolf
Dana G
DG
Saleh
Nivin
N
Biton
Moshe
M
Horwitz
Elad
E
Prokocimer
Zafnat
Z
Prichard
Mark
M
Hahn
Gabriele
G
Goldman-Wohl
Debra
D
Greenfield
Caryn
C
Yagel
Simcha
S
Hengel
Hartmut
H
Altuvia
Yael
Y
Margalit
Hanah
H
Mandelboim
Ofer
O
D020413:3' Untranslated Regions / Q000378:metabolism; D000465:Algorithms; D001665:Binding Sites; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008024:Ligands; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D055655:NK Cell Lectin-Like Receptor Subfamily K; D012367:RNA, Viral / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D014161:Transduction, Genetic
D020413:3' Untranslated Regions; D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; D008024:Ligands; C099187:MHC class I-related chain A; C098080:MICB antigen; D035683:MicroRNAs; D055655:NK Cell Lectin-Like Receptor Subfamily K; D012367:RNA, Viral; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell