Dynamic Co-evolution of Host and Pathogen: HCMV Downregulates the Prevalent Allele MICA*008 to Escape Elimination by NK Cells

Einat Seidel; Vu Thuy Khanh Le; Yotam Bar-On; Pinchas Tsukerman; Jonatan Enk; Rachel Yamin; Natan Stein; Dominik Schmiedel; Esther OiknineDjian; Yiska Weisblum; Boaz Tirosh; Peter Stastny; Dana G. Wolf; Hartmut Hengel; Ofer Mandelboim

doi:10.1016/j.celrep.2015.01.029

Dynamic Co-evolution of Host and Pathogen: HCMV Downregulates the Prevalent Allele MICA*008 to Escape Elimination by NK Cells

Einat Seidel, Vu Thuy Khanh Le, Yotam Bar-On, Pinchas Tsukerman, Jonatan Enk, Rachel Yamin, Natan Stein, Dominik Schmiedel, Esther OiknineDjian, Yiska Weisblum, Boaz Tirosh, Peter Stastny, Dana G. Wolf, Hartmut Hengel, Ofer Mandelboim

The Hebrew University of Jerusalem

Research output: Contribution to journal › Article › peer-review

Abstract

Natural killer (NK) cells mediate innate immune responses against hazardous cells and are particularly important for the control of human cytomegalovirus (HCMV). NKG2D is a key NK activating receptor that recognizes a family of stress-induced ligands, including MICA, MICB, and ULBP1-6. Notably, most of these ligands are targeted by HCMV proteins and a miRNA to prevent the killing of infected cells by NK cells. A particular highly prevalent MICA allele, MICA^*008, is considered to be an HCMV-resistant "escape variant" that confers advantage to human NK cells in recognizing infected cells. However, here we show that HCMV uses its viral glycoprotein US9 to specifically target MICA^*008 and thus escapes NKG2D attack. The finding that HCMV evolved a protein dedicated to countering a single host alleleillustrates the dynamic co-evolution of host and pathogen.

Original language	English
Pages (from-to)	968-982
Number of pages	15
Journal	Cell Reports
Volume	10
Issue number	6
DOIs	https://doi.org/10.1016/j.celrep.2015.01.029
State	Published - 17 Feb 2015

All Science Journal Classification (ASJC) codes

General Biochemistry,Genetics and Molecular Biology

UN SDGs

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

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10.1016/j.celrep.2015.01.029

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Seidel, E., Le, V. T. K., Bar-On, Y., Tsukerman, P., Enk, J., Yamin, R., Stein, N., Schmiedel, D., OiknineDjian, E., Weisblum, Y., Tirosh, B., Stastny, P., Wolf, D. G., Hengel, H., & Mandelboim, O. (2015). Dynamic Co-evolution of Host and Pathogen: HCMV Downregulates the Prevalent Allele MICA*008 to Escape Elimination by NK Cells. Cell Reports, 10(6), 968-982. https://doi.org/10.1016/j.celrep.2015.01.029

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title = "Dynamic Co-evolution of Host and Pathogen: HCMV Downregulates the Prevalent Allele MICA*008 to Escape Elimination by NK Cells",

abstract = "Natural killer (NK) cells mediate innate immune responses against hazardous cells and are particularly important for the control of human cytomegalovirus (HCMV). NKG2D is a key NK activating receptor that recognizes a family of stress-induced ligands, including MICA, MICB, and ULBP1-6. Notably, most of these ligands are targeted by HCMV proteins and a miRNA to prevent the killing of infected cells by NK cells. A particular highly prevalent MICA allele, MICA*008, is considered to be an HCMV-resistant {"}escape variant{"} that confers advantage to human NK cells in recognizing infected cells. However, here we show that HCMV uses its viral glycoprotein US9 to specifically target MICA*008 and thus escapes NKG2D attack. The finding that HCMV evolved a protein dedicated to countering a single host alleleillustrates the dynamic co-evolution of host and pathogen.",

author = "Einat Seidel and Le, {Vu Thuy Khanh} and Yotam Bar-On and Pinchas Tsukerman and Jonatan Enk and Rachel Yamin and Natan Stein and Dominik Schmiedel and Esther OiknineDjian and Yiska Weisblum and Boaz Tirosh and Peter Stastny and Wolf, {Dana G.} and Hartmut Hengel and Ofer Mandelboim",

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doi = "10.1016/j.celrep.2015.01.029",

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Seidel, E, Le, VTK, Bar-On, Y, Tsukerman, P, Enk, J, Yamin, R, Stein, N, Schmiedel, D, OiknineDjian, E, Weisblum, Y , Tirosh, B, Stastny, P, Wolf, DG, Hengel, H & Mandelboim, O 2015, 'Dynamic Co-evolution of Host and Pathogen: HCMV Downregulates the Prevalent Allele MICA*008 to Escape Elimination by NK Cells', Cell Reports, vol. 10, no. 6, pp. 968-982. https://doi.org/10.1016/j.celrep.2015.01.029

TY - JOUR

T1 - Dynamic Co-evolution of Host and Pathogen

T2 - HCMV Downregulates the Prevalent Allele MICA*008 to Escape Elimination by NK Cells

AU - Seidel, Einat

AU - Le, Vu Thuy Khanh

AU - Bar-On, Yotam

AU - Tsukerman, Pinchas

AU - Enk, Jonatan

AU - Yamin, Rachel

AU - Stein, Natan

AU - Schmiedel, Dominik

AU - OiknineDjian, Esther

AU - Weisblum, Yiska

AU - Tirosh, Boaz

AU - Stastny, Peter

AU - Wolf, Dana G.

AU - Hengel, Hartmut

AU - Mandelboim, Ofer

PY - 2015/2/17

Y1 - 2015/2/17

N2 - Natural killer (NK) cells mediate innate immune responses against hazardous cells and are particularly important for the control of human cytomegalovirus (HCMV). NKG2D is a key NK activating receptor that recognizes a family of stress-induced ligands, including MICA, MICB, and ULBP1-6. Notably, most of these ligands are targeted by HCMV proteins and a miRNA to prevent the killing of infected cells by NK cells. A particular highly prevalent MICA allele, MICA*008, is considered to be an HCMV-resistant "escape variant" that confers advantage to human NK cells in recognizing infected cells. However, here we show that HCMV uses its viral glycoprotein US9 to specifically target MICA*008 and thus escapes NKG2D attack. The finding that HCMV evolved a protein dedicated to countering a single host alleleillustrates the dynamic co-evolution of host and pathogen.

AB - Natural killer (NK) cells mediate innate immune responses against hazardous cells and are particularly important for the control of human cytomegalovirus (HCMV). NKG2D is a key NK activating receptor that recognizes a family of stress-induced ligands, including MICA, MICB, and ULBP1-6. Notably, most of these ligands are targeted by HCMV proteins and a miRNA to prevent the killing of infected cells by NK cells. A particular highly prevalent MICA allele, MICA*008, is considered to be an HCMV-resistant "escape variant" that confers advantage to human NK cells in recognizing infected cells. However, here we show that HCMV uses its viral glycoprotein US9 to specifically target MICA*008 and thus escapes NKG2D attack. The finding that HCMV evolved a protein dedicated to countering a single host alleleillustrates the dynamic co-evolution of host and pathogen.

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U2 - 10.1016/j.celrep.2015.01.029

DO - 10.1016/j.celrep.2015.01.029

M3 - مقالة

SN - 2211-1247

VL - 10

SP - 968

EP - 982

JO - Cell Reports

JF - Cell Reports

IS - 6

ER -

Dynamic Co-evolution of Host and Pathogen: HCMV Downregulates the Prevalent Allele MICA*008 to Escape Elimination by NK Cells

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

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