CoChat
Sign Up
Cited by 145Mosquito-borne diseases and controlNeuroinflammation and Neurodegeneration MechanismsVirology and Viral Diseases

Zika virus infection leads to mitochondrial failure, oxidative stress and DNA damage in human iPSC-derived astrocytes

Open access
Ledur, Pítia Flores, Karmirian, Karina, Pedrosa, Carolina da Silva Gouveia, Souza, Leticia Rocha Quintino, Assis-de-Lemos, Gabriela, Martins, Thiago Martino, Ferreira, Jéssica de Cassia Cavalheiro Gomes, de Azevedo Reis, Gabriel Ferreira +17 more·2020·Scientific Reports
DOI 10.1038/s41598-020-57914-xPMC PMC6985105
Open this paper in CoChat — free accountOpen PDF

Abstract

Zika virus (ZIKV) has been extensively studied since it was linked to congenital malformations, and recent research has revealed that astrocytes are targets of ZIKV. However, the consequences of ZIKV infection, especially to this cell type, remain largely unknown, particularly considering integrative studies aiming to understand the crosstalk among key cellular mechanisms and fates involved in the neurotoxicity of the virus. Here, the consequences of ZIKV infection in iPSC-derived astrocytes are presented. Our results show ROS imbalance, mitochondrial defects and DNA breakage, which have been previously linked to neurological disorders. We have also detected glial reactivity, also present in mice and in post-mortem brains from infected neonates from the Northeast of Brazil. Given the role of glia in the developing brain, these findings may help to explain the observed effects in congenital Zika syndrome related to neuronal loss and motor deficit.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41598-020-57914-x

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 87 · Cited by 145

Research works printed but not linked: 80

  1. [1]Kindhauser MK Allen T Frank V Santhana RS Dye C Zika: the origin and spread of a mosquito-borne virus Bull. World Health Organ. 2016 94 675 686C 10.2471/BLT.16.171082 27708473 PMC5034643 · DOI
  2. [2]Dick GWA Kitchen SF Haddow AJ Zika virus. I. Isolations and serological specificity Trans. R. Soc. Trop. Med. Hyg. 1952 46 509 520 10.1016/0035-9203(52)90042-4 12995440 · DOI
  3. [3]Duffy MR Zika virus outbreak on Yap Island, Federated States of Micronesia N. Engl. J. Med. 2009 360 2536 2543 10.1056/NEJMoa0805715 19516034 · DOI
  4. [4]Jouannic J-M Friszer S Leparc-Goffart I Garel C Eyrolle-Guignot D Zika virus infection in French Polynesia Lancet 2016 387 1051 1052 10.1016/S0140-6736(16)00625-5 26944027 · DOI
  5. [5]Faria NR Zika virus in the Americas: Early epidemiological and genetic findings Sci. 2016 352 345 349 10.1126/science.aaf5036 PMC4918795 27013429 · DOI
  6. [6]Wang L From Mosquitos to Humans: Genetic Evolution of Zika Virus Cell Host Microbe 2016 19 561 565 10.1016/j.chom.2016.04.006 27091703 PMC5648540 · DOI
  7. [7]Metsky HC Zika virus evolution and spread in the Americas Nat. 2017 546 411 415 10.1038/nature22402 PMC5563848 28538734 · DOI
  8. [8]Cauchemez S Association between Zika virus and microcephaly in French Polynesia, 2013–15: a retrospective study Lancet 2016 387 2125 2132 10.1016/S0140-6736(16)00651-6 26993883 PMC4909533 · DOI
  9. [9]Cao-Lormeau VM Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study Lancet 2016 387 1531 1539 10.1016/S0140-6736(16)00562-6 26948433 PMC5444521 · DOI
  10. [11]Garcez PP Zika virus impairs growth in human neurospheres and brain organoids Sci. 2016 352 816 818 10.1126/science.aaf6116 27064148 · DOI · Paper page
  11. [12]Ming G-L Tang H Song H Advances in Zika Virus Research: Stem Cell Models, Challenges, and Opportunities Stem Cell 2016 19 690 702 PMC5218815 27912090
  12. [13]Dang J Zika Virus Depletes Neural Progenitors in Human Cerebral Organoids through Activation of the Innate Immune Receptor TLR3 Stem Cell 2016 19 258 265 PMC5116380 27162029
  13. [14]Chimelli L The spectrum of neuropathological changes associated with congenital Zika virus infection Acta Neuropathol. 2017 133 983 999 10.1007/s00401-017-1699-5 28332092 · DOI
  14. [15]Reemst K Noctor SC Lucassen PJ Hol EM The Indispensable Roles of Microglia and Astrocytes during Brain Development Front. Hum. Neurosci. 2016 10 15983 28 10.3389/fnhum.2016.00566 PMC5099170 27877121 · DOI · Paper page
  15. [16]Mlakar J Zika Virus Associated with Microcephaly N. Engl. J. Med. 2016 374 951 958 10.1056/NEJMoa1600651 26862926 · DOI · Paper page
  16. [17]Retallack H Zika virus cell tropism in the developing human brain and inhibition by azithromycin Proc. Natl Acad. Sci. USA 2016 113 14408 14413 10.1073/pnas.1618029113 27911847 PMC5167169 · DOI · Paper page
  17. [18]Simonin Y Zika Virus Strains Potentially Display Different Infectious Profiles in Human Neural Cells EBioMedicine 2016 12 161 169 10.1016/j.ebiom.2016.09.020 27688094 PMC5078617 · DOI
  18. [19]Stefanik M Characterisation of Zika virus infection in primary human astrocytes BMC Neurosci. 2018 19 5 10.1186/s12868-018-0407-2 29463209 PMC5820785 · DOI
  19. [20]Jorgačevski J ZIKV Strains Differentially Affect Survival of Human Fetal Astrocytes versus Neurons and Traffic of ZIKV-Laden Endocytotic Compartments Sci. Rep. 2019 9 8069 10.1038/s41598-019-44559-8 31147629 PMC6542792 · DOI
  20. [21]Potokar M Jorgačevski J Zorec R Astrocytes in Flavivirus Infections IJMS 2019 20 691 16 10.3390/ijms20030691 PMC6386967 30736273 · DOI
  21. [22]Hamel R African and Asian Zika virus strains differentially induce early antiviral responses in primary human astrocytes Infection, Genet. Evolution 2017 49 134 137 10.1016/j.meegid.2017.01.015 28095299 · DOI
  22. [23]Reid C Airo A Hobman T The Virus-Host Interplay: Biogenesis of +RNA Replication Complexes Viruses 2015 7 4385 4413 10.3390/v7082825 26287230 PMC4576186 · DOI
  23. [24]Offerdahl DK Dorward DW Hansen BT Bloom ME Cytoarchitecture of Zika virus infection in human neuroblastoma and Aedes albopictus cell lines Virology 2017 501 54 62 10.1016/j.virol.2016.11.002 27863275 PMC5201448 · DOI
  24. [25]Gladwyn-Ng I Stress-induced unfolded protein response contributes to Zika virus-associated microcephaly Nat. Neurosci. 2018 21 63 71 10.1038/s41593-017-0038-4 29230053 · DOI
  25. [26]Medvedev R Ploen D Hildt E HCV and Oxidative Stress: Implications for HCV Life Cycle and HCV-Associated Pathogenesis Oxid. Med. Cell Longev. 2016 2016 9012580 13 10.1155/2016/9012580 26955431 PMC4756209 · DOI
  26. [27]Fernandez-Garcia M-D Mazzon M Jacobs M Amara A Pathogenesis of Flavivirus Infections: Using and Abusing the Host Cell Cell Host Microbe 2009 5 318 328 10.1016/j.chom.2009.04.001 19380111 · DOI
  27. [28]Li G Characterization of cytopathic factors through genome-wide analysis of the Zika viral proteins in fission yeast Proc. Natl. Acad. Sci. USA 2017 114 E376 E385 10.1073/pnas.1619735114 28049830 PMC5255628 · DOI
  28. [29]Nem de Oliveira Souza I Acute and chronic neurological consequences of early-life Zika virus infection in mice Sci. Transl. Med. 2018 10 eaar2749 10.1126/scitranslmed.aar2749 29875203 · DOI
  29. [30]Souza BSF Zika virus infection induces mitosis abnormalities and apoptotic cell death of human neural progenitor cells Sci. Rep. 2016 6 39775 10.1038/srep39775 28008958 PMC5180086 · DOI
  30. [31]Onorati M Zika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neuroepithelial Stem Cells and Radial Glia CellReports 2016 16 2576 2592 PMC5135012 27568284
  31. [32]Vitale I Galluzzi L Castedo M Kroemer G Mitotic catastrophe: a mechanism for avoiding genomic instability Nat. Rev. Mol. Cell Biol. 2011 12 385 392 10.1038/nrm3115 21527953 · DOI · Paper page
  32. [33]Ryan E Hollingworth R Grand R Activation of the DNA Damage Response by RNA Viruses Biomolecules 2016 6 2 24 10.3390/biom6010002 26751489 PMC4808796 · DOI
  33. [34]Devhare P Meyer K Steele R Ray RB Ray R Zika virus infection dysregulates human neural stem cell growth and inhibits differentiation into neuroprogenitor cells Cell Death Dis. 2017 8 e3106 10.1038/cddis.2017.517 29022904 PMC5682681 · DOI
  34. [35]Garcez PP Zika virus disrupts molecular fingerprinting of human neurospheres Sci. Rep. 2017 7 40780 10.1038/srep40780 28112162 PMC5256095 · DOI
  35. [37]Kuo LJ Yang L-X Gamma-H2AX - a novel biomarker for DNA double-strand breaks Vivo 2008 22 305 309 18610740
  36. [38]Casas, B. S. et al. hiPSC-derived neural stem cells from patients with schizophrenia induce an impaired angiogenesis. Translational Psychiatry 1–15, 10.1038/s41398-018-0095-9 (2018). PMC5821759 29467462 · DOI
  37. [39]Yan Y Efficient and Rapid Derivation of Primitive Neural Stem Cells and Generation of Brain Subtype Neurons From Human Pluripotent Stem Cells STEM CELLS Transl. Med. 2013 2 862 870 10.5966/sctm.2013-0080 24113065 PMC3808201 · DOI
  38. [40]Donald CL Full Genome Sequence and sfRNA Interferon Antagonist Activity of Zika Virus from Recife, Brazil PLoS Negl. Trop. Dis. 2016 10 e0005048 20 10.1371/journal.pntd.0005048 27706161 PMC5051680 · DOI
  39. [41]Filippi-Chiela EC Nuclear morphometric analysis (NMA): screening of senescence, apoptosis and nuclear irregularities PLoS ONE 2012 7 e42522 10.1371/journal.pone.0042522 22905142 PMC3414464 · DOI
  40. [42]Cortese M Ultrastructural Characterization of Zika Virus Replication Factories Cell Reports 2017 18 2113 2123 10.1016/j.celrep.2017.02.014 28249158 PMC5340982 · DOI
  41. [43]Fleury C Mignotte B Vayssière J-L Mitochondrial reactive oxygen species in cell death signaling Biochim. 2002 84 131 141 10.1016/S0300-9084(02)01369-X 12022944 · DOI
  42. [44]Ouyang Y-B Xu L-J Emery JF Lee AS Giffard RG Overexpressing GRP78 influences Ca2+ handling and function of mitochondria in astrocytes after ischemia-like stress MITOCH 2011 11 279 286 10.1016/j.mito.2010.10.007 PMC3037025 21047562 · DOI
  43. [46]Caldecott KW Single-strand break repair and genetic disease Nat. Rev. Genet. 2008 9 619 631 10.1038/nrg2380 18626472 · DOI
  44. [47]Schneider L Fumagalli M di Fagagna FDAA Terminally differentiated astrocytes lack DNA damage response signaling and are radioresistant but retain DNA repair proficiency Cell Death Differ. 2011 19 582 591 10.1038/cdd.2011.129 21979466 PMC3307974 · DOI
  45. [48]Panier S Boulton SJ Double-strand break repair: 53BP1 comes into focus Nat. Rev. Mol. Cell Biol. 2014 15 7 18 10.1038/nrm3719 24326623 · DOI
  46. [49]Nakamura AJ Rao VA Pommier Y Bonner WM The complexity of phosphorylated H2AX foci formation and DNA repair assembly at DNA double-strand breaks Cell Cycle 2014 9 389 397 10.4161/cc.9.2.10475 PMC3086803 20046100 · DOI
  47. [51]Liddelow SA Barres BA Reactive Astrocytes: Production, Function, and Therapeutic Potential Immun. 2017 46 957 967 10.1016/j.immuni.2017.06.006 28636962 · DOI · Paper page
  48. [52]Bender, C., Frik, J. & Gómez, R. M. In Astrocytes 109–124 (Nova Biomedical), 10.13140/2.1.4745.8243 (2012). · DOI
  49. [53]Trindade, P. et al. Short and long TNF-alpha exposure recapitulates canonical astrogliosis events in human induced pluripotent stem cells-derived astrocytes. bioRxiv 1–37, 10.1101/722017 (2019). 32003513 · DOI
  50. [54]Meertens L Axl Mediates ZIKA Virus Entry in Human Glial Cells and Modulates Innate Immune Responses Cell Reports 2017 18 324 333 10.1016/j.celrep.2016.12.045 28076778 · DOI · Paper page
  51. [55]Richard AS AXL-dependent infection of human fetal endothelial cells distinguishes Zika virus from other pathogenic flaviviruses Proc. Natl. Acad. Sci. USA 2017 114 2024 2029 10.1073/pnas.1620558114 28167751 PMC5338370 · DOI
  52. [56]Liu S DeLalio LJ Isakson BE Wang TT AXL-Mediated Productive Infection of Human Endothelial Cells by Zika Virus Novelty and Significance Circ. Res. 2016 119 1183 1189 10.1161/CIRCRESAHA.116.309866 27650556 PMC5215127 · DOI
  53. [57]Wang J Zika virus infected primary microglia impairs NPCs proliferation and differentiation Biochem. Biophys. Res. Commun. 2018 497 619 625 10.1016/j.bbrc.2018.02.118 29453985 · DOI
  54. [58]Smith DR Neuropathogenesis of Zika Virus in a Highly Susceptible Immunocompetent Mouse Model after Antibody Blockade of Type I Interferon PLoS Negl. Trop. Dis. 2017 11 e0005296 10.1371/journal.pntd.0005296 28068342 PMC5249252 · DOI
  55. [59]Sher AA Glover KKM Coombs KM Zika Virus Infection Disrupts Astrocytic Proteins Involved in Synapse Control and Axon Guidance Front. Microbiol. 2019 10 1 20 10.3389/fmicb.2019.00596 30984137 PMC6448030 · DOI
  56. [60]Molofsky AV Astrocytes and disease: a neurodevelopmental perspective Genes. Dev. 2012 26 891 907 10.1101/gad.188326.112 22549954 PMC3347787 · DOI · Paper page
  57. [61]Phatnani, H. & Maniatis, T. Astrocytes in neurodegenerative disease. Cold Spring Harb Perspect Biol7 (2015). PMC4448607 25877220
  58. [62]Seifert G Schilling K Steinhäuser C Astrocyte dysfunction in neurological disorders: a molecular perspective Nat. Rev. Neurosci. 2006 7 194 206 10.1038/nrn1870 16495941 · DOI
  59. [63]Yu CY Hsu YW Liao CL Lin YL Flavivirus Infection Activates the XBP1 Pathway of the Unfolded Protein Response To Cope with Endoplasmic Reticulum Stress J. Virol. 2006 80 11868 11880 10.1128/JVI.00879-06 16987981 PMC1642612 · DOI
  60. [64]Gullberg RC Jordan Steel J Moon SL Soltani E Geiss BJ Oxidative stress influences positive strand RNA virus genome synthesis and capping Virology 2015 475 219 229 10.1016/j.virol.2014.10.037 25514423 PMC4332586 · DOI
  61. [65]Jheng J-R Ho J-Y Horng J-T ER stress, autophagy, and RNA viruses Front. Microbiol. 2014 5 388 10.3389/fmicb.2014.00388 25140166 PMC4122171 · DOI
  62. [66]Blázquez A-B Escribano-Romero E Merino-Ramos T Saiz J-C Martín-Acebes MA Stress responses in flavivirus-infected cells: activation of unfolded protein response and autophagy Front. Microbiol. 2014 5 266 10.3389/fmicb.2014.00266 24917859 PMC4042264 · DOI
  63. [67]Desler C Is There a Link between Mitochondrial Reserve Respiratory Capacity and Aging? J. Aging Res. 2012 2012 1 9 10.1155/2012/192503 PMC3375017 22720157 · DOI
  64. [68]Madigan CA A Macrophage Response to Mycobacterium leprae Phenolic Glycolipid Initiates Nerve Damage in Leprosy Cell 2017 170 973 985.e10 10.1016/j.cell.2017.07.030 28841420 PMC5848073 · DOI
  65. [69]Chandler AL Neural tube defects and maternal intake of micronutrients related to one-carbon metabolism or antioxidant activity Birth Defects Res. Part. A Clin. Mol. Teratol. 2012 94 864 874 10.1002/bdra.23068 22933447 PMC3518275 · DOI
  66. [70]O’Driscoll M Jeggo PA The role of the DNA damage response pathways in brain development and microcephaly: Insight from human disorders DNA Repair. 2008 7 1039 1050 10.1016/j.dnarep.2008.03.018 18458003 · DOI
  67. [71]Mao Z Bozzella M Seluanov A Gorbunova V Comparison of nonhomologous end joining and homologous recombination in human cells DNA Repair. 2008 7 1765 1771 10.1016/j.dnarep.2008.06.018 18675941 PMC2695993 · DOI
  68. [72]van Gent DC Hoeijmakers JH Kanaar R Chromosomal stability and the DNA double-stranded break connection Nat. Rev. Genet. 2001 2 196 206 10.1038/35056049 11256071 · DOI · Paper page
  69. [74]Lambrus BG A USP28–53BP1–p53–p21 signaling axis arrests growth after centrosome loss or prolonged mitosis J. Cell Biol. 2016 214 143 153 10.1083/jcb.201604054 27432896 PMC4949452 · DOI
  70. [75]Nigg EA Holland AJ Once and only once: mechanisms of centriole duplication and their deregulation in disease Nat. Rev. Mol. Cell Biol. 2018 19 297 312 10.1038/nrm.2017.127 29363672 PMC5969912 · DOI
  71. [76]Vitale I Illicit survival of cancer cells during polyploidization and depolyploidization Cell Death Differ. 2010 18 1403 1413 10.1038/cdd.2010.145 21072053 PMC3178421 · DOI · Paper page
  72. [77]Zody MC DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage Nat. 2006 440 1045 1049 10.1038/nature04689 PMC2610434 16625196 · DOI
  73. [78]Mladinich, M. C., Schwedes, J. & Mackow, E. R. Zika Virus Persistently Infects and Is Basolaterally Released from Primary Human Brain Microvascular Endothelial Cells. mBio8, e00952–17–17 (2017). PMC5513708 28698279
  74. [79]Mulkey SB, Arroyave-Wessel M, Peyton C, et al. Neurodevelopmental Abnormalities in Children With In Utero Zika Virus Exposure Without Congenital Zika Syndrome [published online ahead of print, 2020 Jan 6]. JAMA Pediatr. 10.1001/jamapediatrics.2019.5204 (2020). PMC6990858 31904798 · DOI
  75. [80]Schreiner B Astrocyte Depletion Impairs Redox Homeostasis and Triggers Neuronal Loss in the Adult CNS CellReports 2015 12 1377 1384 26299968
  76. [81]Guo C Sun L Chen X Zhang D Oxidative stress, mitochondrial damage and neurodegenerative diseases Neural Regen. Res. 2013 8 2003 2014 25206509 PMC4145906
  77. [82]Bhat AH Oxidative stress, mitochondrial dysfunction and neurodegenerative diseases; a mechanistic insight Biomedicine et. Pharmacotherapy 2015 74 101 110 10.1016/j.biopha.2015.07.025 26349970 · DOI
  78. [83]Sochacki J Generation of iPS cell lines from schizophrenia patients using a non-integrative method Stem Cell Res. 2016 17 97 101 10.1016/j.scr.2016.05.017 27558610 · DOI
  79. [84]Sochacki J Devalle S Reis M Fontenelle LF Rehen S Generation of urine iPS cell line from a patient with obsessive-compulsive disorder using a non-integrative method Stem Cell Res. 2016 17 107 110 10.1016/j.scr.2016.05.018 27558612 · DOI
  80. [86]Singh NP McCoy MT Tice RR Schneider EL A simple technique for quantitation of low levels of DNA damage in individual cells Exp. Cell Res. 1988 175 184 191 10.1016/0014-4827(88)90265-0 3345800 · DOI · Paper page

Authors
Ledur, P. F., Karmirian, K., Pedrosa, C. D. S. G., Souza, L. R. Q., Assis-de-Lemos, G., Martins, T. M., Ferreira, J. D. C. C. G., de Azevedo Reis, G. F., Silva, E. S., Silva, D., Salerno, J. A., Ornelas, I. M., Devalle, S., Madeiro da Costa, R. F., Goto-Silva, L., Higa, L. M., Melo, A., Tanuri, A., Chimelli, L., Murata, M. M., Garcez, P. P., Filippi-Chiela, E. C., Galina, A., Borges, H. L., & Rehen, S. K.
Affiliations
  • D’Or Institute for Research and Education (BR)
  • Universidade Federal do Rio de Janeiro (BR)
  • Instituto Estadual do Cérebro Paulo Niemeyer (BR)
  • Universidade do Estado do Rio de Janeiro (BR)
Corresponding author
Rehen, Stevens Kastrup
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2020-01-27
Volume
10
Issue
1
Pages
1218-1218
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-020-57914-x
PMC
PMC6985105
OpenAlex
W3002961887
Cited by
145
References
87
Citations by year
2026: 11 · 2025: 20 · 2024: 17 · 2023: 25 · 2022: 29 · 2021: 28 · 2020: 15
FWCI
18.19
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Lirias (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-sa)
Funders
  • Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
  • Ministry of Science, Technology and Innovation | Conselho Nacional de Desenvolvimento Científico e Tecnológico
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
Keywords
Zika virus, astrocytes, iPSC-derived astrocytes, mitochondrial dysfunction, oxidative stress, reactive oxygen species, DNA damage, glial activation, congenital Zika syndrome, neurotoxicity, neuronal loss, motor impairment
MeSH terms
Zika Virus Infection, Zika Virus, Animals, Astrocytes, Brain, DNA Damage, Humans, Male, Mice, Inbred C57BL, Mitochondria, Neurons, Oxidative Stress, Mice, Induced Pluripotent Stem Cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review