Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Virally encoded microRNAs (miRNAs) have recently been discoveredin herpesviruses. However, their biological roles are mostlyunknown. We developed an algorithm for the prediction of miRNAtargets and applied it to human cytomegalovirus miRNAs, resultingin the identification of the major histocompatibility complexclass I–related chain B (MICB) gene as a top candidatetarget of hcmv-miR-UL112. MICB is a stress-induced ligand ofthe natural killer (NK) cell activating receptor NKG2D and iscritical for the NK cell killing of virus-infected cells andtumor cells. We show that hcmv-miR-UL112 specifically down-regulatesMICB expression during viral infection, leading to decreasedbinding of NKG2D and reduced killing by NK cells. Our resultsreveal a miRNA-based immunoevasion mechanism that appears tobe exploited by human cytomegalovirus.
1 Lautenberg Center for General and Tumor Immunology, Hebrew University Hadassah Medical School, Jerusalem, Israel. 2 Department of Molecular Genetics and Biotechnology, Hebrew University Hadassah Medical School, Jerusalem, Israel. 3 Institute for Virology, Heinrich Heine University, D40225 Düsseldorf, Germany. 4 Department of Clinical Microbiology and Infectious Diseases, Hadassah University Hospital, Jerusalem, Israel. 5 Department of Pediatrics, University of Alabama, Birmingham, AL 35233, USA 6 Max von Pettenkofer Institut, Department of Virology, D80336 Munich, Germany. 7 Department of Obstetrics and Gynecology, Hadassah Hebrew University Hospital Mount Scopus, Jerusalem, Israel.
* These authors contributed equally to this work.
Present address: Klinikum Ingolstadt, Institut für Laboratoriumsmedizin,D84049 Ingolstadt, Germany.
To whom correspondence should be addressed. E-mail: yaelal{at}md.huji.ac.il (Y.A.); hanahm{at}ekmd.huji.ac.il (H.M.); oferm{at}ekmd.huji.ac.il (O.M.)
Adenovirus E3/19K Promotes Evasion of NK Cell Recognition by Intracellular Sequestration of the NKG2D Ligands Major Histocompatibility Complex Class I Chain-Related Proteins A and B.
B. P. McSharry, H.-G. Burgert, D. P. Owen, R. J. Stanton, V. Prod'homme, M. Sester, K. Koebernick, V. Groh, T. Spies, S. Cox, et al. (2008)
J. Virol.
82, 4585-4594
|Abstract »|Full Text »|PDF »
Suppression of immediate-early viral gene expression by herpesvirus-coded microRNAs: Implications for latency.
E. Murphy, J. Vanicek, H. Robins, T. Shenk, and A. J. Levine (2008)
PNAS
105, 5453-5458
|Abstract »|Full Text »|PDF »
Profiling killers; unravelling the pathways of human natural killer cell function.
G. B. Scott, J. L. Meade, and G. P. Cook (2008)
Brief Funct Genomic Proteomic
|Abstract »|Full Text »|PDF »
Human Cytomegalovirus Regulates Surface Expression of the Viral Protein UL18 by Means of Two Motifs Present in the Cytoplasmic Tail.
M. Maffei, F. Ghiotto, M. Occhino, M. Bono, A. De Santanna, L. Battini, G. L. Gusella, F. Fais, S. Bruno, and E. Ciccone (2008)
J. Immunol.
180, 969-979
|Abstract »|Full Text »|PDF »
Small RNAs and Large DNA Viruses.
J. A. Nelson (2007)
N. Engl. J. Med.
357, 2630-2632
|Full Text »|PDF »
Discrete Clusters of Virus-Encoded MicroRNAs Are Associated with Complementary Strands of the Genome and the 7.2-Kilobase Stable Intron in Murine Cytomegalovirus.
A. H. Buck, J. Santoyo-Lopez, K. A. Robertson, D. S. Kumar, M. Reczko, and P. Ghazal (2007)
J. Virol.
81, 13761-13770
|Abstract »|Full Text »|PDF »
Mouse Cytomegalovirus MicroRNAs Dominate the Cellular Small RNA Profile during Lytic Infection and Show Features of Posttranscriptional Regulation.
L. Dolken, J. Perot, V. Cognat, A. Alioua, M. John, J. Soutschek, Z. Ruzsics, U. Koszinowski, O. Voinnet, and S. Pfeffer (2007)
J. Virol.
81, 13771-13782
|Abstract »|Full Text »|PDF »
Present address: Klinikum Ingolstadt, Institut für Laboratoriumsmedizin, D84049 Ingolstadt, Germany. 
To whom correspondence should be addressed. E-mail: 
