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Evasion of NKG2D-mediated cytotoxic immunity by sarbecoviruses

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Evasion of NKG2D-mediated cytotoxic immunity by sarbecoviruses. / Hartmann, Jordan A; Cardoso, Marcella R; Talarico, Maria Cecilia Ramiro; Kenney, Devin J; Leone, Madison R; Reese, Dagny C; Turcinovic, Jacquelyn; O'Connell, Aoife K; Gertje, Hans P; Marino, Caitlin; Ojeda, Pedro E; De Paula, Erich V; Orsi, Fernanda A; Velloso, Licio Augusto; Cafiero, Thomas R; Connor, John H; Ploss, Alexander; Hoelzemer, Angelique; Carrington, Mary; Barczak, Amy K; Crossland, Nicholas A; Douam, Florian; Boucau, Julie; Garcia-Beltran, Wilfredo F.

in: CELL, Jahrgang 187, Nr. 10, 09.05.2024, S. 2393-2410.e14.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Hartmann, JA, Cardoso, MR, Talarico, MCR, Kenney, DJ, Leone, MR, Reese, DC, Turcinovic, J, O'Connell, AK, Gertje, HP, Marino, C, Ojeda, PE, De Paula, EV, Orsi, FA, Velloso, LA, Cafiero, TR, Connor, JH, Ploss, A, Hoelzemer, A, Carrington, M, Barczak, AK, Crossland, NA, Douam, F, Boucau, J & Garcia-Beltran, WF 2024, 'Evasion of NKG2D-mediated cytotoxic immunity by sarbecoviruses', CELL, Jg. 187, Nr. 10, S. 2393-2410.e14. https://doi.org/10.1016/j.cell.2024.03.026

APA

Hartmann, J. A., Cardoso, M. R., Talarico, M. C. R., Kenney, D. J., Leone, M. R., Reese, D. C., Turcinovic, J., O'Connell, A. K., Gertje, H. P., Marino, C., Ojeda, P. E., De Paula, E. V., Orsi, F. A., Velloso, L. A., Cafiero, T. R., Connor, J. H., Ploss, A., Hoelzemer, A., Carrington, M., ... Garcia-Beltran, W. F. (2024). Evasion of NKG2D-mediated cytotoxic immunity by sarbecoviruses. CELL, 187(10), 2393-2410.e14. https://doi.org/10.1016/j.cell.2024.03.026

Vancouver

Hartmann JA, Cardoso MR, Talarico MCR, Kenney DJ, Leone MR, Reese DC et al. Evasion of NKG2D-mediated cytotoxic immunity by sarbecoviruses. CELL. 2024 Mai 9;187(10):2393-2410.e14. https://doi.org/10.1016/j.cell.2024.03.026

Bibtex

@article{0e0227f09de9445c8690bf01b3e61f44,
title = "Evasion of NKG2D-mediated cytotoxic immunity by sarbecoviruses",
abstract = "SARS-CoV-2 and other sarbecoviruses continue to threaten humanity, highlighting the need to characterize common mechanisms of viral immune evasion for pandemic preparedness. Cytotoxic lymphocytes are vital for antiviral immunity and express NKG2D, an activating receptor conserved among mammals that recognizes infection-induced stress ligands (e.g., MIC-A/B). We found that SARS-CoV-2 evades NKG2D recognition by surface downregulation of MIC-A/B via shedding, observed in human lung tissue and COVID-19 patient serum. Systematic testing of SARS-CoV-2 proteins revealed that ORF6, an accessory protein uniquely conserved among sarbecoviruses, was responsible for MIC-A/B downregulation via shedding. Further investigation demonstrated that natural killer (NK) cells efficiently killed SARS-CoV-2-infected cells and limited viral spread. However, inhibition of MIC-A/B shedding with a monoclonal antibody, 7C6, further enhanced NK-cell activity toward SARS-CoV-2-infected cells. Our findings unveil a strategy employed by SARS-CoV-2 to evade cytotoxic immunity, identify the culprit immunevasin shared among sarbecoviruses, and suggest a potential novel antiviral immunotherapy.",
keywords = "Humans, SARS-CoV-2/immunology, Killer Cells, Natural/immunology, NK Cell Lectin-Like Receptor Subfamily K/metabolism, COVID-19/immunology, Immune Evasion, Histocompatibility Antigens Class I/immunology, Animals, Cytotoxicity, Immunologic, Down-Regulation, Lung/immunology",
author = "Hartmann, {Jordan A} and Cardoso, {Marcella R} and Talarico, {Maria Cecilia Ramiro} and Kenney, {Devin J} and Leone, {Madison R} and Reese, {Dagny C} and Jacquelyn Turcinovic and O'Connell, {Aoife K} and Gertje, {Hans P} and Caitlin Marino and Ojeda, {Pedro E} and {De Paula}, {Erich V} and Orsi, {Fernanda A} and Velloso, {Licio Augusto} and Cafiero, {Thomas R} and Connor, {John H} and Alexander Ploss and Angelique Hoelzemer and Mary Carrington and Barczak, {Amy K} and Crossland, {Nicholas A} and Florian Douam and Julie Boucau and Garcia-Beltran, {Wilfredo F}",
note = "Copyright {\textcopyright} 2024 Elsevier Inc. All rights reserved.",
year = "2024",
month = may,
day = "9",
doi = "10.1016/j.cell.2024.03.026",
language = "English",
volume = "187",
pages = "2393--2410.e14",
journal = "CELL",
issn = "0092-8674",
publisher = "Cell Press",
number = "10",

}

RIS

TY - JOUR

T1 - Evasion of NKG2D-mediated cytotoxic immunity by sarbecoviruses

AU - Hartmann, Jordan A

AU - Cardoso, Marcella R

AU - Talarico, Maria Cecilia Ramiro

AU - Kenney, Devin J

AU - Leone, Madison R

AU - Reese, Dagny C

AU - Turcinovic, Jacquelyn

AU - O'Connell, Aoife K

AU - Gertje, Hans P

AU - Marino, Caitlin

AU - Ojeda, Pedro E

AU - De Paula, Erich V

AU - Orsi, Fernanda A

AU - Velloso, Licio Augusto

AU - Cafiero, Thomas R

AU - Connor, John H

AU - Ploss, Alexander

AU - Hoelzemer, Angelique

AU - Carrington, Mary

AU - Barczak, Amy K

AU - Crossland, Nicholas A

AU - Douam, Florian

AU - Boucau, Julie

AU - Garcia-Beltran, Wilfredo F

N1 - Copyright © 2024 Elsevier Inc. All rights reserved.

PY - 2024/5/9

Y1 - 2024/5/9

N2 - SARS-CoV-2 and other sarbecoviruses continue to threaten humanity, highlighting the need to characterize common mechanisms of viral immune evasion for pandemic preparedness. Cytotoxic lymphocytes are vital for antiviral immunity and express NKG2D, an activating receptor conserved among mammals that recognizes infection-induced stress ligands (e.g., MIC-A/B). We found that SARS-CoV-2 evades NKG2D recognition by surface downregulation of MIC-A/B via shedding, observed in human lung tissue and COVID-19 patient serum. Systematic testing of SARS-CoV-2 proteins revealed that ORF6, an accessory protein uniquely conserved among sarbecoviruses, was responsible for MIC-A/B downregulation via shedding. Further investigation demonstrated that natural killer (NK) cells efficiently killed SARS-CoV-2-infected cells and limited viral spread. However, inhibition of MIC-A/B shedding with a monoclonal antibody, 7C6, further enhanced NK-cell activity toward SARS-CoV-2-infected cells. Our findings unveil a strategy employed by SARS-CoV-2 to evade cytotoxic immunity, identify the culprit immunevasin shared among sarbecoviruses, and suggest a potential novel antiviral immunotherapy.

AB - SARS-CoV-2 and other sarbecoviruses continue to threaten humanity, highlighting the need to characterize common mechanisms of viral immune evasion for pandemic preparedness. Cytotoxic lymphocytes are vital for antiviral immunity and express NKG2D, an activating receptor conserved among mammals that recognizes infection-induced stress ligands (e.g., MIC-A/B). We found that SARS-CoV-2 evades NKG2D recognition by surface downregulation of MIC-A/B via shedding, observed in human lung tissue and COVID-19 patient serum. Systematic testing of SARS-CoV-2 proteins revealed that ORF6, an accessory protein uniquely conserved among sarbecoviruses, was responsible for MIC-A/B downregulation via shedding. Further investigation demonstrated that natural killer (NK) cells efficiently killed SARS-CoV-2-infected cells and limited viral spread. However, inhibition of MIC-A/B shedding with a monoclonal antibody, 7C6, further enhanced NK-cell activity toward SARS-CoV-2-infected cells. Our findings unveil a strategy employed by SARS-CoV-2 to evade cytotoxic immunity, identify the culprit immunevasin shared among sarbecoviruses, and suggest a potential novel antiviral immunotherapy.

KW - Humans

KW - SARS-CoV-2/immunology

KW - Killer Cells, Natural/immunology

KW - NK Cell Lectin-Like Receptor Subfamily K/metabolism

KW - COVID-19/immunology

KW - Immune Evasion

KW - Histocompatibility Antigens Class I/immunology

KW - Animals

KW - Cytotoxicity, Immunologic

KW - Down-Regulation

KW - Lung/immunology

U2 - 10.1016/j.cell.2024.03.026

DO - 10.1016/j.cell.2024.03.026

M3 - SCORING: Journal article

C2 - 38653235

VL - 187

SP - 2393-2410.e14

JO - CELL

JF - CELL

SN - 0092-8674

IS - 10

ER -