Evidence map›Paper›PMID 34688984›Full record

ReviewCurrent opinion in virology2021

Viral Z-RNA triggers ZBP1-dependent cell death.

Siddharth Balachandran, Edward S Mocarski

Open access · greenAbstract readReview
In one paragraph

Review in Current opinion in virology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
4.7field-weighted citation impact, top 4% 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

61 citing papers in PubMed, 79 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Role of PANoptosis in intestinal diseases and its therapeutic implications.Journal of molecular medicine (Berlin, Germany) · 2026
    Review
  6. Review
  7. Article
  8. PPP1R3G-RIPK1-ZBP1 axis activates early-stage apoptosis and late-stage necroptosis to promote doxorubicin-induced cardiotoxicity.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  9. Telomere Crisis Shapes Cancer Evolution.Cold Spring Harbor perspectives in biology · 2026
    Review
  10. Article
  11. Review
  12. Review
  13. Characterization of Z-DNA dynamics across the tree of life.bioRxiv : the preprint server for biology · 2025
    Article
  14. Article
  15. PARP12-mediated mono-ADP-ribosylation as a checkpoint for necroptosis and apoptosis.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  16. Article
  17. Coronavirus endoribonuclease antagonizes ZBP1-mediated necroptosis and delays multiple cell death pathways.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  18. Review
  19. Review
  20. Article

1 more citing papers are in PubMed but not listed here.

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

2 authors at 2 institutions in 1 country.

Siddharth BalachandranBlood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA. Electronic address: siddharth.balachandran@fccc.edu.
Edward S MocarskiDepartment of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, 30322, USA. Electronic address: mocarski@emory.edu.
Emory Healthcare · USFox Chase Cancer Center · US

Funding

WORD PROCESSING CENTER--COREP30CA006927 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI Dietmar J Kappes · 1985 to 2026
$138.8M
Mechanism, Function, and Exploitation of Influenza A Virus-Activated Cell DeathR01AI135025 · NIAID · RESEARCH INST OF FOX CHASE CAN CTR · PI BALACHANDRAN, SIDDHARTH · 2017 to 2025
$6.8M
CYTOMEGALOVIRUS DNA REPLICATION AND RECOMBINATIONR01AI020211 · NIAID · STANFORD UNIVERSITY · PI EDWARD S MOCARSKI, EDWARD S. · 1985 to 2021
$5.9M
Targeting RIPK3 in Flu-Associated Lung InjuryR01AI144400 · NIAID · RESEARCH INST OF FOX CHASE CAN CTR · PI BALACHANDRAN, SIDDHARTH, CUNY, GREGORY D · 2019 to 2023
$3.6M
NCI NIH HHS P30 CA006927NIAID NIH HHS R01 AI020211NIAID NIH HHS R01 AI135025NIAID NIH HHS R01 AI144400
6 · The paper itself

Abstract

Z-DNA Binding protein 1 (ZBP1) activates Receptor Interacting Protein Kinase 3 (RIPK3) -dependent cell death during lytic infection by members of the orthomyxovirus, herpesvirus and poxvirus families. ZBP1 possesses two Zα domains capable of selective binding to Z-DNA, as well as to Z-RNA. We have now unveiled Z-RNA as the ligand that activates ZBP1 in cells infected with orthomyxoviruses (influenza A and B viruses) and the poxvirus vaccinia virus (VACV). Orthomyxovirus Z-RNA is sensed by ZBP1 in the nucleus of infected cells, resulting in nuclear activation of RIPK3, consequent rupture of the nucleus, and hyper-inflammatory 'nuclear necroptosis'. VACV-generated Z-RNA accumulates in the cytoplasm, where it is sequestered from ZBP1 by E3, the viral E3L gene product. In viruses where the E3 Zα domain has been mutated, ZBP1 senses Z-RNA and triggers RIPK3-dependent necroptosis in the cytoplasm. Z-RNA is thus a new viral pathogen-associated molecular pattern (PAMP).

Indexed as

Influenza A virusInfluenza B virusNecroptosisNucleic Acid ConformationVaccinia virusAnimalsHumansPathogen-Associated Molecular Pattern MoleculesReceptor-Interacting Protein Serine-Threonine KinasesRNA-Binding ProteinsRNA, ViralViral ProteinsPathogen-Associated Molecular Pattern MoleculesReceptor-Interacting Protein Serine-Threonine KinasesRIPK3 protein, humanRNA-Binding ProteinsRNA, ViralViral ProteinsZBP1 protein, human

Identifiers

PMID34688984
PMCPMC8643332
OpenAlexW3208065423

What OpenQuestion holds

Textmetadata
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.