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^*

^*Corresponding author for this work

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

64 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
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

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Publisher Copyright:
© 2015 The Authors.

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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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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

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

Abstract

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