Evidence map›Paper›PMID 31142589›Full record

ArticleThe Journal of experimental medicine2019

The complex of MCMV proteins and MHC class I evades NK cell control and drives the evolution of virus-specific activating Ly49 receptors.

Jelena Železnjak, Vanda Juranić Lisnić, Branka Popović, Berislav Lisnić, Marina Babić, Anne Halenius, Anne L'Hernault, Tihana Lenac Roviš, Hartmut Hengel, Florian Erhard and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

17 citing papers in PubMed, 21 citations in OpenAlex.

  1. Unconventional CD8Science advances · 2025
    Article
  2. Review
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  4. Diverse cytomegalovirus US11 antagonism and MHC-A evasion strategies reveal a tit-for-tat coevolutionary arms race in hominids.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  5. Decoding murine cytomegalovirus.PLoS pathogens · 2023
    Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. The role of NK cells in fighting the virus infection and sepsis.International journal of medical sciences · 2021
    Review
  14. Article
  15. Review
  16. Article
  17. Article
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

15 authors at 6 institutions in 5 countries.

Jelena Železnjak *Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
Vanda Juranić Lisnić *Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
Branka PopovićDepartment of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
Berislav LisnićDepartment of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
Marina BabićDepartment of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.ORCID 0000-0003-0747-7074
Anne HaleniusInstitute of Virology, Medical Center University of Freiburg, Freiburg, Germany.ORCID 0000-0001-6335-1017
Anne L'HernaultPrecision Medicine and Genomics, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Cambridge, UK.
Tihana Lenac RovišDepartment of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
Hartmut HengelInstitute of Virology, Medical Center University of Freiburg, Freiburg, Germany.ORCID 0000-0002-3482-816X
Florian ErhardInstitute of Virology and Immunobiology, Julius Maximilian University of Würzburg, Würzburg, Germany.
Alec J RedwoodInstitute for Respiratory Health, University of Western Australia, Western Australia, Australia.ORCID 0000-0001-8601-8292
Silvia M VidalDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.
Lars DölkenInstitute of Virology and Immunobiology, Julius Maximilian University of Würzburg, Würzburg, Germany.
Astrid Krmpotić *Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
Stipan Jonjić *Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia stipan.jonjic@uniri.hr.ORCID 0000-0001-5003-3108
University of Rijeka · HRUniversity of Freiburg · DEUniversity of Würzburg · DEAstraZeneca (United Kingdom) · GBMcGill University · CAThe University of Western Australia · AU

Funding

Medical Research Council G1002523
6 · The paper itself

Abstract

CMVs efficiently target MHC I molecules to avoid recognition by cytotoxic T cells. However, the lack of MHC I on the cell surface renders the infected cell susceptible to NK cell killing upon missing self recognition. To counter this, mouse CMV (MCMV) rescues some MHC I molecules to engage inhibitory Ly49 receptors. Here we identify a new viral protein, MATp1, that is essential for MHC I surface rescue. Rescued altered-self MHC I molecules show increased affinity to inhibitory Ly49 receptors, resulting in inhibition of NK cells despite substantially reduced MHC I surface levels. This enables the virus to evade recognition by licensed NK cells. During evolution, this novel viral immune evasion mechanism could have prompted the development of activating NK cell receptors that are specific for MATp1-modified altered-self MHC I molecules. Our study solves a long-standing conundrum of how MCMV avoids recognition by NK cells, unravels a fundamental new viral immune evasion mechanism, and demonstrates how this forced the evolution of virus-specific activating MHC I-restricted Ly49 receptors.

Indexed as

AnimalsAntigens, LyCytotoxicity, ImmunologicDisease Models, AnimalFemaleFibroblastsHerpesviridae InfectionsHistocompatibility Antigens Class IImmune EvasionKiller Cells, NaturalMaleMiceMice, Inbred BALB CMice, Inbred C57BLMice, TransgenicMuromegalovirusAntigens, LyHistocompatibility Antigens Class INatural Cytotoxicity Triggering Receptor 1Ncr1 protein, mouseNK Cell Lectin-Like Receptor Subfamily AViral Proteins

Identifiers

PMID31142589
PMCPMC6683999
OpenAlexW2946985211

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.