Host immune system gene targeting by a viral miRNA

Noam Stern-Ginossar, Naama Elefant, Albert Zimmermann, Dana G. Wolf, Nivin Saleh, Moshe Biton, Elad Horwitz, Zafnat Prokocimer, Mark Prichard, Gabriele Hahn, Debra Goldman-Wohl, Caryn Greenfield, Simcha Yagel, Hartmut Hengel, Yael Altuvia*, Hanah Margalit, Ofer Mandelboim

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

552 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)376-381
Number of pages6
JournalScience
Volume317
Issue number5836
DOIs
StatePublished - 20 Jul 2007

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