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

Internal Medicine

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

56 Scopus citations

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 (US)
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 - Feb 17 2015

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

Access to Document

10.1016/j.celrep.2015.01.029

Cite this

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

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

@article{6e78355dcb7e48358e1b18840bef5877,

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",

note = "Funding Information: We thank Cosima Zimmermann for providing HCMV stocks. This study was supported by the European Research Council under the European Union{\textquoteright}s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement number 320473-BacNK BacNK and by the European Union FP7 grant-316655 (VACTRAIN). Additional support came from the I-CORE Program of the Planning and Budgeting Committee and the Israel Science Foundation and by the I-Core on Chromatin and RNA in Gene Regulation, the GIF Foundation, the Lewis Family Foundation, the Israel Cancer Research Fund professorship grant, the Israeli Science Foundation, the Helmholtz Israel grant and the Rosetrees Trust (all to O.M.) and VISTRIE VH-VI-242 (to H.H.). O.M. is a Crown Professor of Molecular Immunology. E.S. is supported by the Adams Fellowship Programme of the Israel Academy of Sciences and Humanities and by the Foulkes Foundation. D.S. receives funding from the People Programme (Marie Curie Actions) of the European Union{\textquoteright}s Seventh Framework Programme FP7 (FP7-PEOPLE-2012-ITN-317013). Publisher Copyright: {\textcopyright} 2015 The Authors.",

year = "2015",

month = feb,

day = "17",

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

language = "English (US)",

volume = "10",

pages = "968--982",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "6",

}

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

N1 - Funding Information: We thank Cosima Zimmermann for providing HCMV stocks. This study was supported by the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement number 320473-BacNK BacNK and by the European Union FP7 grant-316655 (VACTRAIN). Additional support came from the I-CORE Program of the Planning and Budgeting Committee and the Israel Science Foundation and by the I-Core on Chromatin and RNA in Gene Regulation, the GIF Foundation, the Lewis Family Foundation, the Israel Cancer Research Fund professorship grant, the Israeli Science Foundation, the Helmholtz Israel grant and the Rosetrees Trust (all to O.M.) and VISTRIE VH-VI-242 (to H.H.). O.M. is a Crown Professor of Molecular Immunology. E.S. is supported by the Adams Fellowship Programme of the Israel Academy of Sciences and Humanities and by the Foulkes Foundation. D.S. receives funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme FP7 (FP7-PEOPLE-2012-ITN-317013). Publisher Copyright: © 2015 The Authors.

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.

UR - http://www.scopus.com/inward/record.url?scp=84923087527&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923087527&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2015.01.029

DO - 10.1016/j.celrep.2015.01.029

M3 - Article

C2 - 25683719

AN - SCOPUS:84923087527

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

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this