The human cytomegalovirus microRNA miR-UL112 acts synergistically with a cellular microRNA to escape immune elimination.
Although approximately 200 viral microRNAs are known, only very few share similar targets with their host's microRNAs. A notable example of this is the stress-induced ligand MICB, which is targeted by several distinct viral and cellular microRNAs. Through the investigation of the microRNA-mediated immune-evasion strategies of herpesviruses, we initially identified two new cellular microRNAs that targeted MICB and were expressed differently both in healthy tissues and during melanocyte transformation. We show that coexpression of various pairs of cellular microRNAs interfered with the downregulation of MICB, whereas the viral microRNAs optimized their targeting ability to efficiently downregulate MICB. Moreover, we demonstrate that through site proximity and possibly inhibition of translation, a human cytomegalovirus (HCMV) microRNA acts synergistically with a cellular microRNA to suppress MICB expression during HCMV infection.
Nachmani
Daphna
D
The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
Lankry
Dikla
D
Wolf
Dana G
DG
Mandelboim
Ofer
O
D045744:Cell Line, Tumor; D003587:Cytomegalovirus / Q000276:immunology*; D015536:Down-Regulation; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006367:HeLa Cells; D004854:Herpesvirus 4, Human; D019288:Herpesvirus 8, Human; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D007694:Killer Cells, Natural / Q000276:immunology; D035683:MicroRNAs / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; C098080:MICB antigen; D035683:MicroRNAs