Evidence map›Paper›PMID 38653235›Full record

ArticleCell2024

Evasion of NKG2D-mediated cytotoxic immunity by sarbecoviruses.

Jordan A Hartmann, Marcella R Cardoso, Maria Cecilia Ramiro Talarico, Devin J Kenney, Madison R Leone, Dagny C Reese, Jacquelyn Turcinovic, Aoife K O'Connell, Hans P Gertje, Caitlin Marino and 14 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.6field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 15 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors at 7 institutions in 3 countries.

Jordan A HartmannRagon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA.
Marcella R CardosoRagon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA.
Maria Cecilia Ramiro TalaricoRagon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA.
Devin J KenneyDepartment of Virology, Immunology, and Microbiology, Chobanian and Avedisian Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
Madison R LeoneRagon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA.
Dagny C ReeseRagon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA.
Jacquelyn TurcinovicNational Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
Aoife K O'ConnellNational Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
Hans P GertjeNational Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
Caitlin MarinoRagon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA.
Pedro E OjedaRagon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA.
Erich V De PaulaSchool of Medical Sciences, University of Campinas, Campinas, SP, Brazil; Hematology and Hemotherapy Center, University of Campinas, Campinas, SP, Brazil.
Fernanda A OrsiSchool of Medical Sciences, University of Campinas, Campinas, SP, Brazil; Hematology and Hemotherapy Center, University of Campinas, Campinas, SP, Brazil.
Licio Augusto VellosoSchool of Medical Sciences, University of Campinas, Campinas, SP, Brazil; Obesity and Comorbidities Research Center, University of Campinas, Campinas, SP, Brazil.
Thomas R CafieroDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.
John H ConnorNational Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
Alexander PlossDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.
Angelique HoelzemerFirst Department of Medicine, Division of Infectious Diseases, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany; Institute for Infection and Vaccine Development (IIRVD), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany; Research Department Virus Immunology, Leibniz Institute for Virology, Hamburg, Germany.
Mary CarringtonRagon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA; Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA; Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Amy K BarczakRagon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Nicholas A CrosslandDepartment of Virology, Immunology, and Microbiology, Chobanian and Avedisian Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA; Department of Pathology and Laboratory Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Florian DouamDepartment of Virology, Immunology, and Microbiology, Chobanian and Avedisian Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
Julie BoucauRagon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA. Electronic address: jboucau@mgh.harvard.edu.
Wilfredo F Garcia-BeltranRagon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA, USA. Electronic address: wgarciabeltran@mgh.harvard.edu.
Boston University · USMassachusetts General Hospital · USRagon Institute of MGH, MIT and Harvard · USUniversidade Estadual de Campinas (UNICAMP) · BRHarvard University · USPrinceton University · USUniversität Hamburg · DE

Funding

WORK ORDER 126643 B539 EXPAND IC SUITE75N91019D00024 · NIAID · LEIDOS BIOMEDICAL RESEARCH, INC. · PI BRISCOE, LYNN · 2019 to 2025
$3932.6M
The impact of HIV viral diversity and cellular immunity on HIV pathogenesisP30AI060354 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI ARTHUR Y KIM · 2004 to 2026
$94.4M
RESEARCH TRAINING IN IMMUNOLOGYT32AI007309 · NIAID · BOSTON UNIVERSITY MEDICAL CAMPUS · PI GUMMULURU, SURYARAM · 1988 to 2024
$7.4M
Genetic Viral and Host Adaptations to Breach Species Barriers of HCVR01AI107301 · NIAID · PRINCETON UNIVERSITY · PI Thomas Pietschmann, Alexander Ploss · 2013 to 2026
$6.0M
Host genetic resistance to COVID-19ZIABC011949 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI CARRINGTON, MARY N. · 2020 to 2025
$997k
Vectra Polaris Quantitative Pathology Imaging SystemS10OD030269 · OD · BOSTON UNIVERSITY MEDICAL CAMPUS · PI CROSSLAND, NICHOLAS ALEXANDER · 2021 to 2021
$402k
Ventana Discovery Ultra Research Autostainer: an Ex+ Core serviceS10OD026983 · OD · BOSTON UNIVERSITY MEDICAL CAMPUS · PI CROSSLAND, NICHOLAS ALEXANDER · 2019 to 2019
$207k
NCI NIH HHS 75N91019D00024NIAID NIH HHS P30 AI060354NIAID NIH HHS R01 AI107301NIAID NIH HHS T32 AI007309NIH HHS S10 OD026983NIH HHS S10 OD030269
6 · The paper itself

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.

Indexed as

COVID-19Immune EvasionKiller Cells, NaturalNK Cell Lectin-Like Receptor Subfamily KSARS-CoV-2AnimalsCytotoxicity, ImmunologicDown-RegulationHistocompatibility Antigens Class IHumansLungHistocompatibility Antigens Class IKLRK1 protein, humanMHC class I-related chain AMICB antigenNK Cell Lectin-Like Receptor Subfamily KCOVID-19cytotoxiclymphocytesMIC-A/BNK cellsNKG2DsarbecovirusesSARS-CoV-2

Identifiers

PMID38653235
PMCPMC11088510
OpenAlexW4394998551

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.