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

doi:10.1126/science.1140956

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 journal › Article › peer-review

565 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 language	English
Pages (from-to)	376-381
Number of pages	6
Journal	Science
Volume	317
Issue number	5836
DOIs	https://doi.org/10.1126/science.1140956
State	Published - 20 Jul 2007

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1126/science.1140956

Cite this

@article{d3746be10b8f4798a06571909b8a5ac3,

title = "Host immune system gene targeting by a viral miRNA",

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.",

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

year = "2007",

month = jul,

day = "20",

doi = "10.1126/science.1140956",

language = "אנגלית",

volume = "317",

pages = "376--381",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "5836",

}

TY - JOUR

T1 - Host immune system gene targeting by a viral miRNA

AU - Stern-Ginossar, Noam

AU - Elefant, Naama

AU - Zimmermann, Albert

AU - Wolf, Dana G.

AU - Saleh, Nivin

AU - Biton, Moshe

AU - Horwitz, Elad

AU - Prokocimer, Zafnat

AU - Prichard, Mark

AU - Hahn, Gabriele

AU - Goldman-Wohl, Debra

AU - Greenfield, Caryn

AU - Yagel, Simcha

AU - Hengel, Hartmut

AU - Altuvia, Yael

AU - Margalit, Hanah

AU - Mandelboim, Ofer

PY - 2007/7/20

Y1 - 2007/7/20

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34547132780&partnerID=8YFLogxK

U2 - 10.1126/science.1140956

DO - 10.1126/science.1140956

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 17641203

AN - SCOPUS:34547132780

SN - 0036-8075

VL - 317

SP - 376

EP - 381

JO - Science

JF - Science

IS - 5836

ER -

Host immune system gene targeting by a viral miRNA

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this