Host Immune System Gene Targeting by a Viral miRNA

Noam Stern‐Ginossar(Hebrew University of Jerusalem), Naama Elefant(Hebrew University of Jerusalem), Albert Zimmermann(Hebrew University of Jerusalem), Dana G. Wolf(Hebrew University of Jerusalem), Nivin Saleh(Hebrew University of Jerusalem), Moshe Biton(Hebrew University of Jerusalem), E. Philip Horwitz(Hebrew University of Jerusalem), Zafnat Prokocimer(Hebrew University of Jerusalem), Mark N. Prichard(Hebrew University of Jerusalem), Gabriele Hahn(Hebrew University of Jerusalem), Debra Goldman‐Wohl(Hebrew University of Jerusalem), Caryn Greenfield(Hebrew University of Jerusalem), Simcha Yagel(Hebrew University of Jerusalem), Hartmut Hengel(Hebrew University of Jerusalem), Yaël Altuvia(Hebrew University of Jerusalem), Hanah Margalit(Hebrew University of Jerusalem), Ofer Mandelboim(Hebrew University of Jerusalem)
Science
July 19, 2007
10.1126/science.1140956
Cited by 642

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.

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