The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein
Open accessAbstract
Macrophages and dendritic cells have key roles in viral infections, providing virus reservoirs that frequently resist antiviral therapies and linking innate virus detection to antiviral adaptive immune responses. Human immunodeficiency virus 1 (HIV-1) fails to transduce dendritic cells and has a reduced ability to transduce macrophages, due to an as yet uncharacterized mechanism that inhibits infection by interfering with efficient synthesis of viral complementary DNA. In contrast, HIV-2 and related simian immunodeficiency viruses (SIVsm/mac) transduce myeloid cells efficiently owing to their virion-associated Vpx accessory proteins, which counteract the restrictive mechanism. Here we show that the inhibition of HIV-1 infection in macrophages involves the cellular SAM domain HD domain-containing protein 1 (SAMHD1). Vpx relieves the inhibition of lentivirus infection in macrophages by loading SAMHD1 onto the CRL4(DCAF1) E3 ubiquitin ligase, leading to highly efficient proteasome-dependent degradation of the protein. Mutations in SAMHD1 cause Aicardi-Goutières syndrome, a disease that produces a phenotype that mimics the effects of a congenital viral infection. Failure to dispose of endogenous nucleic acid debris in Aicardi-Goutières syndrome results in inappropriate triggering of innate immune responses via cytosolic nucleic acids sensors. Thus, our findings show that macrophages are defended from HIV-1 infection by a mechanism that prevents an unwanted interferon response triggered by self nucleic acids, and uncover an intricate relationship between innate immune mechanisms that control response to self and to retroviral pathogens.
Overview
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.
Integrity signals
Registry
Cites
Statistics
Verification
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.
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?
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“This approach was necessary because PU.1 is the master transcriptional regulator necessary for macrophage differentiation and silencing PU.1 prior to infection results in a change in the cellular phenotype that causes resistance to HIV infection72,73.”
From HIV-1 Vpr combats the PU.1-driven antiviral response in primary human macrophages (2024) · cites this paper as [73]
Experimental — accuracy not yet measuredIn the citing paper
“It was then determined that Vpx may facilitate the association of SAMHD1 with this complex to promote its proteasome-dependent degradation.”
From Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection (2016) · cites this paper as [81]
In the citing paper
“Upon MS analysis, the cellular innate immune protein SAMHD1 was the most spectrally abundant association with the Vpx-E3 ubiquitin ligase complex.”
From Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection (2016) · cites this paper as [81]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
In Vivo Gene Delivery and Stable Transduction of Nondividing Cells by a Lentiviral Vector
Naldini, L., Blömer, U., Gallay, P., Ory, D., Mulligan, R., Gage, F. H., Verma, I. M., & Trono, D. (1996) · Science · doi:10.1126/science.272.5259.263 · Cited by 4,903
Trex1 prevents cell-intrinsic initiation of autoimmunity
Stetson, D. B., Ko, J. S., Heidmann, T., & Medzhitov, R. (2008) · Cell · doi:10.1016/j.cell.2008.06.032 · Cited by 1,280
Dendritic Cells: Translating Innate to Adaptive Immunity
Steinman, R. M., & Hemmi, H. (2006) · Springer eBooks · doi:10.1007/3-540-32636-7_2 · Cited by 855
A quantitative assay for HIV DNA integration in vivo
Butler, S. L., Hansen, M. S., & Bushman, F. D. (2001) · Nature Medicine · doi:10.1038/87979 · Cited by 695
Rice, G., Bond, J., Asipu, A., Brunette, R. L., Manfield, I. W., Carr, I., Fuller, J. C., Jackson, R. M., Lamb, T., Briggs, T. A., et al. (2009) · Nature Genetics · doi:10.1038/ng.373 · Cited by 686
Molecular architecture and assembly of the DDB1–CUL4A ubiquitin ligase machinery
Angers, S., Li, T., Yi, X., MacCoss, M. J., Moon, R. T., & Zheng, N. (2006) · Nature · doi:10.1038/nature05175 · Cited by 674
The Challenge of Viral Reservoirs in HIV-1 Infection
Blankson, J. N., Persaud, D., & Siliciano, R. F. (2002) · Annual Review of Medicine · doi:10.1146/annurev.med.53.082901.104024 · Cited by 649 · cited 1×
“MDM were subjected to RNAi targeting DCAF1, SAMHD1 or non-targeting RNAi (NT1, NT2), and infected (1) or not (2) with SIV VLP loaded with SIVmac Vpx, 2 days later.”
MethodTrex1 Exonuclease Degrades ssDNA to Prevent Chronic Checkpoint Activation and Autoimmune Disease
Yang, Y., Lindahl, T. L., & Barnes, D. E. (2007) · Cell · doi:10.1016/j.cell.2007.10.017 · Cited by 574
Yan, N., Regalado-Magdos, A. D., Stiggelbout, B., Lee‐Kirsch, M. A., & Lieberman, J. (2010) · Nature Immunology · doi:10.1038/ni.1941 · Cited by 522
A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells
Manel, N., Hogstad, B., Wang, Y., Levy, D. E., Unutmaz, D., & Littman, D. R. (2010) · Nature · doi:10.1038/nature09337 · Cited by 427
Flagged first, then by citations
Cited by
Sorted by citations
Aicardi–Goutières syndrome and the type I interferonopathies
Crow, Y. J., & Manel, N. (2015) · Nature Reviews Immunology · doi:10.1038/nri3850 · Cited by 925
Lahouassa, H., Daddacha, W., Hofmann, H., Ayinde, D., Logue, E. C., Dragin, L., Bloch, N., Maudet, C., Bertrand, M., Gramberg, T., et al. (2012) · Nature Immunology · doi:10.1038/ni.2236 · Cited by 852
HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase
Goldstone, D. C., Ennis-Adeniran, V., Hedden, J. J., Groom, H. C. T., Rice, G., Christodoulou, E., Walker, P. A., Kelly, G. P., Haire, L. F., Yap, M. W., et al. (2011) · Nature · doi:10.1038/nature10623 · Cited by 871
HIV infection: epidemiology, pathogenesis, treatment, and prevention
Maartens, G., Celum, C., & Lewin, S. R. (2014) · The Lancet · doi:10.1016/s0140-6736(14)60164-1 · Cited by 913
SAMHD1 restricts HIV-1 infection in resting CD4+ T cells
Baldauf, H., Pan, X., Erikson, E., Schmidt, S., Daddacha, W. B., Burggraf, M., Schenková, K., Ambiel, I., Wabnitz, G. H., Gramberg, T., et al. (2012) · Nature Medicine · doi:10.1038/nm.2964 · Cited by 636
Rules of engagement: molecular insights from host–virus arms races
Daugherty, M. D., & Malik, H. S. (2012) · Annual Review of Genetics · doi:10.1146/annurev-genet-110711-155522 · Cited by 515
Human MX2 is an interferon-induced post-entry inhibitor of HIV-1 infection
Goujon, C., Moncorgé, O., Bauby, H., Doyle, T., Ward, C. C., Schaller, T., Hué, S., Barclay, W., Schulz, R., & Malim, M. H. (2013) · Nature · doi:10.1038/nature12542 · Cited by 632
Interferon-inducible effector mechanisms in cell-autonomous immunity
MacMicking, J. D. (2012) · Nature reviews. Immunology · doi:10.1038/nri3210 · Cited by 588
Yan, N., & Chen, Z. J. (2012) · Nature Immunology · doi:10.1038/ni.2229 · Cited by 565
“2, 566–573 (2010). 46.”
Pestal, K., Funk, C. C., Snyder, J. M., Price, N. D., Treuting, P. M., & Stetson, D. B. (2015) · Immunity · doi:10.1016/j.immuni.2015.11.001 · Cited by 514
“Similarly, SAMHD1 is a dNTP phosphohydrolase that prevents cDNA synthesis by retroviral reverse transcriptase enzymes, strongly suggesting that the cGAS-STING pathway also drives autoimmunity in AGS caused by SAMHD1 mutations (Goldstone et al., 2011; Hrecka et al., 2011; Laguette et al., 2011; Rehwinkel et al., 2013).”
BackgroundHIV Restriction Factors and Mechanisms of EvasionPreprint
Malim, M. H., & Bieniasz, P. D. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006940 · Cited by 517
“Indeed, two groups very recently reported using proteomic methods to identify SAMHD1 (sterile a motif domain-, HD domain-containing protein 1) as the myeloid-specific, degradable cellular target of HIV-2/SIVsm Vpx proteins (Hrecka et al. 2011; Laguette et al. 2011).”
BackgroundSAMHD1 acts at stalled replication forks to prevent interferon induction
Coquel, F., Silva, M. J., Técher, H., Zadorozhny, K., Sharma, S., Nieminuszczy, J., Mettling, C., Dardillac, E., Barthe, A., Schmitz, A.-L., et al. (2018) · Nature · doi:10.1038/s41586-018-0050-1 · Cited by 455
The structural biology of HIV-1: mechanistic and therapeutic insights
Engelman, A., & Cherepanov, P. (2012) · Nature Reviews Microbiology · doi:10.1038/nrmicro2747 · Cited by 499
Lahaye, X., Satoh, T., Gentili, M., Cerboni, S., Conrad, C., Hurbain, I., El Marjou, A., Lacabaratz, C., Lelièvre, J.-D., & Manel, N. (2013) · Immunity · doi:10.1016/j.immuni.2013.11.002 · Cited by 390
“, 2010), which is imposed by the restriction factor SAMHD1 (Hrecka et al., 2011; Laguette et al., 2011), an Aicardi-Goutières Syndrome (AGS) susceptibility gene (Rice et al.”
InfluentialType I interferonopathies: a novel set of inborn errors of immunity
Crow, Y. J. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2011.06220.x · Cited by 412
Phosphorylation of SAMHD1 by Cyclin A2/CDK1 Regulates Its Restriction Activity toward HIV-1
Cribier, A., Descours, B., Valadão, A. L. C., Laguette, N., & Benkirane, M. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.03.017 · Cited by 391
“These cellular factors mediate a cellintrinsic resistance that arrest the viral life cycle at a specific step (Hrecka et al., 2011; Kirchhoff, 2010; Laguette et al., 2011; Malim and Bieniasz, 2012).”
BackgroundInfluentialEvolutionary conflicts between viruses and restriction factors shape immunity
Duggal, N. K., & Emerman, M. (2012) · Nature reviews. Immunology · doi:10.1038/nri3295 · Cited by 384
“In addition, the antiviral activity of restriction factors is sometimes specific to families of viruses.”
BackgroundInfluentialThe role of ubiquitylation in immune defence and pathogen evasion
Jiang, X., & Chen, Z. J. (2011) · Nature reviews. Immunology · doi:10.1038/nri3111 · Cited by 352
Studies of endogenous retroviruses reveal a continuing evolutionary saga
Stoye, J. P. (2012) · Nature Reviews Microbiology · doi:10.1038/nrmicro2783 · Cited by 350
Powell, R. D., Holland, P. J., Hollis, T., & Perrino, F. W. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.c111.317628 · Cited by 358
Animal models for HIV/AIDS research
Hatziioannou, T., & Evans, D. T. (2012) · Nature Reviews Microbiology · doi:10.1038/nrmicro2911 · Cited by 378
HIV-1 transcription and latency: an update
Lint, C. M. V., Bouchat, S., & Marcello, A. (2013) · Retrovirology · doi:10.1186/1742-4690-10-67 · Cited by 352
“ies by the Benkirane’s group and Skowronski’s group, SAMHD1 was recently described as the restriction factor that blocks HIV-1 infection of non-cycling myeloid cells [185,186].”
BackgroundSAMHD1 restricts HIV-1 reverse transcription in quiescent CD4+T-cells
Descours, B., Cribier, A., Chable-Bessia, C., Ayinde, D., Rice, G., Crow, Y. J., Yatim, A., Schwartz, O., Laguette, N., & Benkirane, M. (2012) · Retrovirology · doi:10.1186/1742-4690-9-87 · Cited by 363
“Interestingly, the Aicardi-Goutières syndrome gene product SAMHD1 was recently described as the restriction factor that blocks HIV-1 infection of non-cycling myeloid cells [11-13].”
BackgroundMethodAtkins, J. F., Loughran, G., Bhatt, P. R., Firth, A. E., & Baranov, P. V. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw530 · Cited by 330
“dNTP depletion is part of the hosts response to viral infection and lentiviruses, such as HIV-2, have developed a vpx gene to counteract this effect (100,101).”
BackgroundTransmission of innate immune signaling by packaging of cGAMP in viral particles
Gentili, M., Kowal, J., Tkach, M., Satoh, T., Lahaye, X., Conrad, C., Boyron, M., Lombard, B., Durand, S., Kroemer, G., et al. (2015) · Science · doi:10.1126/science.aab3628 · Cited by 341
White, T. E., Brandariz-Núñez, A., Valle‐Casuso, J. C., Amie, S. M., Nguyen, L. A., Kim, B., Tuzova, M. N., & Diaz‐Griffero, F. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.03.005 · Cited by 324
“Although the variant HD206AA, which targets the active site of SAMHD1, loses retroviral restriction (Hrecka et al., 2011; Laguette et al., 2011), its oligomerization capacity is also defective, making it difficult to pinpoint which defect causes loss of restriction (White et al.”
BackgroundInfluentialNatural SIV Hosts: Showing AIDS the Door
Chahroudi, A., Bosinger, S. E., Vanderford, T. H., Paiardini, M., & Silvestri, G. (2012) · Science · doi:10.1126/science.1217550 · Cited by 317
“newly described SAMHD1 host restriction factor in myeloid cells (63, 64) and further exploration of the impact of this virus-host interaction, as well as other such interactions --in particular that of BST-2 tetherin with several viral gene products (65)-- is the subject of ongoing research in the natural host field.”
Hartmann, G. (2017) · Advances in Immunology · doi:10.1016/bs.ai.2016.11.001 · Cited by 285
“SAMHD1 was identified as a potent restriction factor for HIV (Hrecka et al., 2011; Laguette et al., 2011; Simon, Bloch, & Landau, 2015), other non- human retroviruses (Gramberg et al., 2013), and herpesviruses, including HSV-1 (Hollenbaugh et al., 2013; Kim, White, Brandariz-Nunez, Diaz- Griffero, & Weitzman, 2013).”
BackgroundInfluentialThe Restriction Factors of Human Immunodeficiency Virus
Harris, R. S., Hultquist, J. F., & Evans, D. T. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.r112.416925 · Cited by 306
“Vpx serves as a scaffold for the formation of an E3 ubiquitin ligase complex consisting of DCAF1, DDB1, and CUL4, which combine to promote the polyubiquitination and degradation of SAMHD1 (79, 80, 86).”
BackgroundComparing HIV‐1 and HIV‐2 infection: Lessons for viral immunopathogenesis
Nyamweya, S., Hegedus, A., Jaye, A., Rowland-Jones, S. L., Flanagan, K. L., & Macallan, D. C. (2013) · Reviews in Medical Virology · doi:10.1002/rmv.1739 · Cited by 328
“The effect of SAMHD1 onHIV-1 strains is therefore to restrict their replication in dendritic and myeloid cells; HIV-2 strains, by contrast, escape such restriction because they possess Vpx [88,89].”
BackgroundInfluentialHIV-1 and interferons: who's interfering with whom?
Doyle, T., Goujon, C., & Malim, M. H. (2015) · Nature Reviews Microbiology · doi:10.1038/nrmicro3449 · Cited by 307
Macrophages and their relevance in Human Immunodeficiency Virus Type I infection
Koppensteiner, H., Brack‐Werner, R., & Schindler, M. (2012) · Retrovirology · doi:10.1186/1742-4690-9-82 · Cited by 305
“partly restored by Vpu nor does HIV-1 Vpr contain the ability to antagonize SamHD1 [41,126].”
BackgroundThe Developmental Control of Transposable Elements and the Evolution of Higher Species
Friedli, M., & Trono, D. (2015) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100814-125514 · Cited by 274
The ribonuclease activity of SAMHD1 is required for HIV-1 restriction
Ryoo, J., Choi, J., Oh, C., Kim, S., Seo, M., Kim, S., Seo, D., Kim, J., White, T. E., Brandariz-Núñez, A., et al. (2014) · Nature Medicine · doi:10.1038/nm.3626 · Cited by 294
Franzolin, E., Pontarin, G., Rampazzo, C., Miazzi, C., Ferraro, P., Palumbo, E., Reichard, P. A., & Bianchi, V. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1312033110 · Cited by 279
“Other lentiviruses escape restriction by coinfection with a protein (Vpx) targeting SAMHD1 for ubiquitin-dependent degradation (6, 7).”
BackgroundThe enemy within: endogenous retroelements and autoimmune disease
Volkman, H. E., & Stetson, D. B. (2014) · Nature Immunology · doi:10.1038/ni.2872 · Cited by 333
Lim, E. S., Fregoso, O. I., McCoy, C. O., Matsen, F. A., IV, Malik, H. S., & Emerman, M. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.01.004 · Cited by 271
“Binding of Diverse Vprs to SAMHD1 Correlates with Degradation Previous studies have shown that Vpx from SIVsm and HIV-2 are able to bind SAMHD1 directly in order to promote its degradation (Hrecka et al., 2011; Laguette et al., 2011).”
InfluentialIntrinsic host restrictions to HIV-1 and mechanisms of viral escape
Simon, V. R., Bloch, N., & Landau, N. R. (2015) · Nature Immunology · doi:10.1038/ni.3156 · Cited by 273
Bacterial origins of human cell-autonomous innate immune mechanisms
Wein, T., & Sorek, R. (2022) · Nature reviews. Immunology · doi:10.1038/s41577-022-00705-4 · Cited by 241
Sowd, G. A., Serrao, E., Wang, H., Wang, W., Fadel, H. J., Poeschla, E. M., & Engelman, A. N. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1524213113 · Cited by 249
“Single-round MLV-Luc was expressed using pFb-Luc, pCG-MLV-gagpol, and pHCMV-VSV-G (4) whereas pSIV3+ and pCG-VPX were used to generate Vpx-containing virus like particles (55).”
MethodGentili, M., Lahaye, X., Nadalin, F., Nader, G. P. F., Lombardi, E. P., Hervé, S., Silva, N. S. D., Rookhuizen, D. C., Zueva, E., Goudot, C., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.01.105 · Cited by 256
“We next efficiently transduced DCs using Vpx to overcome SAMHD1 restriction (Hrecka et al., 2011; Laguette et al., 2011) (Figure S2A).”
MethodIzquierdo-Useros, N., Lorizate, M., Puertas, M. C., Rodriguez-Plata, M. T., Zangger, N., Erikson, E., Pino, M., Erkizia, I., Glass, B., Clotet, B., et al. (2012) · PLoS Biology · doi:10.1371/journal.pbio.1001448 · Cited by 244
“In the first approach, we transduced DCs with lentiviral particles coding for different shRNAs by co-infection with vpxexpressing lentiviruses to counteract the restriction factor SAMHD1 and facilitate DC productive infection.”
BackgroundBerger, A., Sommer, A. F. R., Zwarg, J., Hamdorf, M., Welzel, K., Esly, N., Panitz, S., Reuter, A., Ramos, I., Jatiani, A., et al. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002425 · Cited by 260
“. Two recent publications identified Sterile Alpha Motif (SAM) Domain and HD domain-containing protein 1 (SAMHD1) as the Vpx-sensitive restriction factor that inhibits HIV-1 infection of macrophages and dendritic cells”
BackgroundHuman Genetic Determinants of Viral Diseases
Kenney, A. D., Dowdle, J. A., Bozzacco, L., McMichael, T. M., Gelais, C. S., Panfil, A. R., Sun, Y., Schlesinger, L. S., Anderson, M. Z., Green, P. L., et al. (2017) · Annual Review of Genetics · doi:10.1146/annurev-genet-120116-023425 · Cited by 244
“SAMHD1 is a newly discovered HIV-1 restriction factor that can be counteracted by Vpx protein from HIV-2 and certain simian immunodeficiency viruses (59, 82, 137).”
BackgroundCD32a is a marker of a CD4 T-cell HIV reservoir harbouring replication-competent proviruses
Descours, B., Petitjean, G., López-Zaragoza, J.-L., Bruel, T., Raffel, R., Psomas, C. K., Reynes, J., Lacabaratz, C., Lévy, Y., Schwartz, O., et al. (2017) · Nature · doi:10.1038/nature21710 · Cited by 256
Innate immunity against HIV-1 infection
Altfeld, M. A., & Gale, M. (2015) · Nature Immunology · doi:10.1038/ni.3157 · Cited by 260
HIV-1 infection of human macrophages directly induces viperin which inhibits viral production
Nasr, N., Maddocks, S., Turville, S. G., Harman, A. N., Woolger, N., Helbig, K. J., Wilkinson, J. C., Bye, C. R., Wright, T. K., Rambukwelle, D., et al. (2012) · Blood · doi:10.1182/blood-2012-01-407395 · Cited by 247
Clifford, R. M., Louis, T., Robbe, P., Ackroyd, S., Burns, A., Timbs, A., Colopy, G. W., Dreau, H. M.-P., Sigaux, F., Judde, J. G., et al. (2013) · Blood · doi:10.1182/blood-2013-04-490847 · Cited by 240
Intracellular Nucleic Acid Detection in Autoimmunity
Crowl, J. T., Gray, E. E., Pestal, K., Volkman, H. E., & Stetson, D. B. (2017) · Annual Review of Immunology · doi:10.1146/annurev-immunol-051116-052331 · Cited by 222
“Two years later, two groups identified SAMHD1 as the essential myeloid restriction factor for HIV-1 that is targeted for degradation by the Vpx accessory protein of HIV-2 (82, 83).”
BackgroundHIV-1 Latency in Monocytes/Macrophages
Kumar, A., Abbas, W., & Herbein, G. (2014) · Viruses · doi:10.3390/v6041837 · Cited by 214
“Lahouassa, H.; Daddacha, W.; Hofmann, H.; Ayinde, D.; Logue, E.C.; Dragin, L.; Bloch, N.; Maudet, C.; Bertrand, M.; Gramberg, T.; et al. SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates.”
BackgroundInfluentialHIV Latency Is Established Directly and Early in Both Resting and Activated Primary CD4 T Cells
Chávez, L., Calvanese, V., & Verdin, E. M. (2015) · PLoS Pathogens · doi:10.1371/journal.ppat.1004955 · Cited by 225
“Vpx is a lentiviral accessory protein encoded by HIV-2 that degrades SAMHD1 and thereby allows the virus to infect many cell types—resting CD4 T cells [28], dendritic cells, monocytes, and macrophages [50, 51]—that are usually off limits to Role of T Cell Activation in Establishment of HIV Latency”
BackgroundBeloglazova, N. G., Flick, R., Tchigvintsev, A., Brown, G., Popovic, A., Nocek, B. P., & Yakunin, A. F. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.431148 · Cited by 228
“SAMHD1 also restricts HIV-1 replication by depleting the intracellular dNTP pool and is counteracted by the HIV-2 accessory protein Vpx (4, 5, 21).”
BackgroundInfluentialAPOBEC3A Is a Specific Inhibitor of the Early Phases of HIV-1 Infection in Myeloid Cells
Berger, G., Durand, S., Fargier, G., Nguyen, X.-N., Cordeil, S., Bouaziz, S., Muriaux, D. M., Darlix, J., & Cimarelli, A. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002221 · Cited by 216
“Despite the fact that SAMHD1 is expressed in different cell types, it seems to restrict lentiviral infection specifically in myeloid cells, probably highlighting the need for a particular cellular context, or for specific cellular partners [59,60].”
BackgroundInfluentialKim, B., Nguyen, L. A., Daddacha, W. B., & Hollenbaugh, J. A. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.c112.374843 · Cited by 209
“Vpx promotes the DCAF1 E3 ubiquitin ligase-mediated degradation of SAMHD1 (6, 7).”
BackgroundResultPQBP1 Is a Proximal Sensor of the cGAS-Dependent Innate Response to HIV-1
Yoh, S. M., Schneider, M., Seifried, J., Soonthornvacharin, S., Akleh, R. E., Olivieri, K. C., Jesus, P. D. D., Ruan, C., de Castro, E., Ruiz, P. A., et al. (2015) · Cell · doi:10.1016/j.cell.2015.04.050 · Cited by 209
“The experimental models in this report have relied on the introduction of Vpx, which alleviates the block of early reverse transcription at the minus strand strong stop in highly restrictive cells, such as DCs (Hrecka et al., 2011; Laguette et al., 2011).”
Modulation of LINE-1 and Alu/SVA Retrotransposition by Aicardi-Goutières Syndrome-Related SAMHD1
Zhao, K., Du, J., Han, X., Goodier, J. L., Li, P., Zhou, X., Wei, W., Evans, S. L., Li, L., Zhang, W., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.08.019 · Cited by 194
“Similar L1 inhibition was observed when the expression of endogenous SAMHD1 was reduced by using a SIV Vpx (viral protein X) expression vector, but not by a mutant VpxQ76A expression vector (defective in mediating SAMHD1 degradation; Wei et al., 2012) in HEK293T cells (Figures S2E and S2F).”
InfluentialThe Role of Macrophages in HIV-1 Persistence and Pathogenesis
Kruize, Z., & Kootstra, N. A. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.02828 · Cited by 205
“…(nucleosides and triphosphates), in turn reducing the dNTPs pool and thereby limiting the reverse transcriptase activity (Berger A. et al., 2011; Hrecka et al., 2011; Laguette et al., 2011; Lahouassa et al., 2012); Myxovirusresistance protein 2 (MX2) which inhibits HIV-1 replication post entry…”
BackgroundSAMHD1 Promotes DNA End Resection to Facilitate DNA Repair by Homologous Recombination
Daddacha, W. B., Koyen, A. E., Bastien, A. J., Head, P. E., Dhere, V. R., Nabeta, G. N., Connolly, E. C., Werner, E., Madden, M. Z., Daly, M. B., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.08.008 · Cited by 197
“SAMHD1 is targeted for proteasomal degradation by the retrovirus accessory protein Vpx (Hrecka et al., 2011; Laguette et al., 2011), and virus-like particles (VLPs) containing Vpx have been used to sensitize acute myelogenous leukemia cells to cytarabine chemotherapy (Herold et al., 2017;…”
BackgroundInfluentialMolecular insights into NF2/Merlin tumor suppressor function
Cooper, J. M., & Giancotti, F. G. (2014) · FEBS Letters · doi:10.1016/j.febslet.2014.04.001 · Cited by 191
“Vpr- and Vpxmediated targeting of SAMHD1 and the uracil DNA glycosylase UNG2 direct these proteins to proteasomal degradation [91,99].”
BackgroundGelais, C. S., de Silva, S., Amie, S. M., Coleman, C. M., Hoy, H., Hollenbaugh, J. A., Kim, B.-J., & Wu, L. J. (2012) · Retrovirology · doi:10.1186/1742-4690-9-105 · Cited by 201
“Vpxmediated degradation of SAMHD1 accounts for the enhanced HIV-1 infection in myeloid cells [11-13,16].”
BackgroundResultInfluentialType I interferonopathies: Mendelian type I interferon up-regulation
Crow, Y. J. (2014) · Current Opinion in Immunology · doi:10.1016/j.coi.2014.10.005 · Cited by 194
García‐Mesa, Y., Jay, T. R., Checkley, M. A., Luttge, B. G., Dobrowolski, C. N., Valadkhan, S., Landreth, G. E., Karn, J., & Alvarez-Carbonell, D. (2016) · Journal of NeuroVirology · doi:10.1007/s13365-016-0499-3 · Cited by 184
“It is particularly important to understand the susceptibility of microglial cells to HIV infection because peripheral macrophages are poorly infected by HIV due restrictions imposed by the SAMHD1 protein (Hrecka et al. 2011).”
Ahn, J., Hao, C., Yan, J., DeLucia, M., Mehrens, J., Wang, C., Gronenborn, A. M., & Skowroński, J. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.340711 · Cited by 203
“2, human SAMHD1 co-precipitatedDCAF1 and DDB1 efficiently, only in the presence of Vpx, as we reported previously (compare lane 2 with lane 3, (8)).”
BackgroundMethodInfluentialSelf-citationPuryear, W. B., Akiyama, H., Geer, S. D., Ramirez, N. P., Yu, X., Reinhard, B. M., & Gummuluru, S. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003291 · Cited by 181
“In addition to the observation that HIV-1 fusion to DCs dramatically declines upon maturation [61], intracellular environment of DCs is antagonistic to productive virus replication, presumably because of presence of SAMHD1 and other yet-to-be defined IFN-induced myeloid cell-specific antiviral factors [62,63,64,65].”
BackgroundLiu, R., Li, J., Zhang, T., Zou, L., Chen, Y., Wang, K., Lei, Y., Yuan, K., Li, Y., Lan, J., et al. (2014) · Autophagy · doi:10.4161/auto.28912 · Cited by 178
SAMHD1 is a biomarker for cytarabine response and a therapeutic target in acute myeloid leukemia
Schneider, C., Oellerich, T., Baldauf, H., Schwarz, S.-M., Thomas, D., Flick, R., Bohnenberger, H., Kaderali, L., Stegmann, L., Cremer, A., et al. (2016) · Nature Medicine · doi:10.1038/nm.4255 · Cited by 183
Laguette, N., Rahm, N., Sobhian, B., Chable-Bessia, C., Münch, J., Snoeck, J., Sauter, D., Switzer, W. M., Heneine, W., Kirchhoff, F., et al. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.01.007 · Cited by 184
Dolan, M.-J., Therrien, M., Jereb, S., Kamath, T., Gazestani, V., Atkeson, T., Marsh, S. E., Goeva, A., Lojek, N. M., Murphy, S., et al. (2023) · Nature Immunology · doi:10.1038/s41590-023-01558-2 · Cited by 185
“Transduction of monocytes with lentiviruses is facilitated by the SIV-encoded protein Vpx 38,39 , which degrades SAMHD1, a restriction factor that prevents reverse transcription of lentiviral RNA 40,41 .”
BackgroundIFITM Proteins Restrict HIV-1 Infection by Antagonizing the Envelope Glycoprotein
Yu, J., Li, M., Wilkins, J. M., Ding, S., Swartz, T. H., Esposito, A. M., Zheng, Y.-M., Freed, E. O., Liang, C., Chen, B. K., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.08.055 · Cited by 183
“Among these, APOBEC3G, TRIM5a, Tetherin or Bst2, SAMHD1, and MxB have been reported as potent anti-HIV restriction factors (Goujon et al., 2013; Hrecka et al., 2011; Kane et al., 2013; Laguette et al., 2011; Liu et al., 2013; Neil et al., 2008; Sadler and Williams, 2008; Sheehy et al., 2002;…”
Restriction Factors: From Intrinsic Viral Restriction to Shaping Cellular Immunity Against HIV-1
Colomer-Lluch, M., Ruiz, A., Moris, A., & Prado, J. G. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02876 · Cited by 185
“Some myeloid cells—monocytes, macrophages, and DCs— and CD4+ T cells ubiquitously express SAMHD1 (4, 6, 69), which regulates their cell cycle by controlling the availability of the dNTP pools.”
BackgroundMacrophages and HIV-1: An Unhealthy Constellation
Sattentau, Q. J., & Stevenson, M. (2016) · Cell Host & Microbe · doi:10.1016/j.chom.2016.02.013 · Cited by 172
Mechanism of allosteric activation of SAMHD1 by dGTP
Ji, X., Wu, Y. G., Yan, J., Mehrens, J., Yang, H., DeLucia, M., Hao, C., Gronenborn, A. M., Skowroński, J., Ahn, J., et al. (2013) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2692 · Cited by 168
Self-citationHost and Viral Determinants of Mx2 Antiretroviral Activity
Busnadiego, I., Kane, M., Rihn, S. J., Preugschas, H. F., Hughes, J., Blanco-Melo, D., Strouvelle, V. P., Zang, T. M., Willett, B. J., Boutell, C., et al. (2014) · Journal of Virology · doi:10.1128/jvi.00214-14 · Cited by 160
“SAMHD1 is likely to be similarly important in this regard (6, 7).”
LINE-1 protein localization and functional dynamics during the cell cycle
Mita, P., Wudzinska, A., Sun, X., Andrade, J., Nayak, S., Kahler, D. J., Badri, S., LaCava, J., Ueberheide, B., Yun, C. Y., et al. (2018) · eLife · doi:10.7554/elife.30058 · Cited by 142
“Indeed, SAMHD1 expression was found to restrict replication of lentiviruses such as HIV, by restricting availability of dNTPs (Hrecka et al., 2011; Goldstone et al., 2011).”
BackgroundPeng, K., Muranyi, W., Glass, B., Laketa, V., Yant, S. R., Tsai, L. K., Cihlář, T., Müller, B., & Kräusslich, H. (2014) · eLife · doi:10.7554/elife.04114 · Cited by 155
“Furthermore, the cellular restriction factor SAMHD1 inhibits HIV-1 replication in primary macrophages at the stage of reverse transcription (Hrecka et al., 2011).”
BackgroundHost Factor SAMHD1 Restricts DNA Viruses in Non-Dividing Myeloid Cells
Hollenbaugh, J. A., Gee, P., Baker, J. L., Daly, M. B., Amie, S. M., Tate, J., Kasai, N., Kanemura, Y., Kim, D., Ward, B. M., et al. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003481 · Cited by 157
“A series of recent studies highlighted SAMHD1, a cellular dNTP triphosphohydrolase, as an anti-lentiviral restriction factor predominantly found in myeloid cells [5,6,7,8,24,40,52].”
BackgroundInfluentialBehrendt, R., Schumann, T., Gerbaulet, A., Nguyen, L. A., Schubert, N., Alexopoulou, D., Berka, U., Lienenklaus, S., Peschke, K., Sutter, K., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.07.037 · Cited by 161
“The Vpx accessory protein of many SIV strains and HIV-2 counteracts this restriction by targeting SAMHD1 for proteasomal degradation (Hrecka et al., 2011; Laguette et al., 2011).”
InfluentialNuclear import of the HIV-1 core precedes reverse transcription and uncoating
Selyutina, A., Persaud, M., Lee, K., KewalRamani, V., & Diaz-Griffero, F. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108201 · Cited by 144
“Next, we measured nuclear import of HIV-1 capsid in cells expressing the restriction factor SAMHD1, which is nuclear and inhibits RT (Hrecka et al., 2011; Laguette et al., 2011).”
Tetramerization of SAMHD1 Is Required for Biological Activity and Inhibition of HIV Infection
Yan, J., Kaur, S., DeLucia, M., Hao, C., Mehrens, J., Wang, C., Golczak, M., Palczewski, K., Gronenborn, A. M., Ahn, J., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.443796 · Cited by 159
“Because C terminus mutations modulate SAMHD1 function, it is likely that Vpx binding to the C terminus will also affect SAMHD1 catalytic activity, for instance, by altering its tetrameric state.”
BackgroundMethodInfluentialSelf-citationSAMHD1‐dependent retroviral control and escape in mice
Rehwinkel, J., Maelfait, J., Bridgeman, A., Rigby, R. E., Hayward, B. E., Liberatore, R. A., Bieniasz, P. D., Towers, G. J., Moita, L. F., Crow, Y. J., et al. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.163 · Cited by 159
“Consistent with that model, SAMHD1 depletion by Vpx delivery or RNA interference renders many human myeloid cells and resting T cells more permissive to HIV-1 infection (Berger et al , 2011; Hrecka et al , 2011; Laguette et al , 2011; Baldauf et al , 2012; Descours et al , 2012; Kim et al , 2012; Lahouassa et al , 201…”
InfluentialSAMHD1 prevents autoimmunity by maintaining genome stability
Kretschmer, S., Wolf, C., König, N., Staroske, W., Guck, J. R., Häusler, M., Luksch, H., Nguyen, L. A., Kim, B., Alexopoulou, D., et al. (2014) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2013-204845 · Cited by 163
MARCH8 inhibits HIV-1 infection by reducing virion incorporation of envelope glycoproteins
Tada, T., Zhang, Y., Koyama, T., Tobiume, M., Tsunetsugu‐Yokota, Y., Yamaoka, S., Fujita, H., & Tokunaga, K. (2015) · Nature Medicine · doi:10.1038/nm.3956 · Cited by 158
Welbourn, S., Dutta, S. M., Semmes, O. J., & Strebel, K. (2013) · Journal of Virology · doi:10.1128/jvi.01642-13 · Cited by 161
“In susceptible cell types, SAMHD1 has been shown to restrict infection of these lentiviruses at the reverse transcription step, and Vpx counteracts this restriction by binding to and causing the proteasomal degradation of SAMHD1 via interaction with a Cul4/DDB1/DCAF1 ubiquitin-ligase complex (2, 3, 11).”
BackgroundDNA sensor cGAS-mediated immune recognition
Xia, P., Wang, S., Gao, P., Gao, G., & Fan, Z. (2016) · Protein & Cell · doi:10.1007/s13238-016-0320-3 · Cited by 154
“However, HIV-2 encodes Vpx that mediates SAMHD1 degradation through the CRL4-DCAF1 E3 ubiquitin ligase, resulting in HIV-2 replication in DCs and macrophages (Hrecka et al., 2011; Laguette et al., 2011).”
BackgroundRole of SAMHD1 nuclear localization in restriction of HIV-1 and SIVmac
Brandariz-Núñez, A., Valle‐Casuso, J. C., White, T. E., Laguette, N., Benkirane, M., Brojatsch, J., & Diaz‐Griffero, F. (2012) · Retrovirology · doi:10.1186/1742-4690-9-49 · Cited by 158
“Mechanistic studies have suggested that Vpx induces the proteasomal degradation of SAMHD1[17,18].”
BackgroundYurkovetskiy, L., Guney, M. H., Kim, K., Goh, S. L., McCauley, S. M., Dauphin, A., Diehl, W. E., & Luban, J. (2018) · Nature Microbiology · doi:10.1038/s41564-018-0256-x · Cited by 149
Restrictions to HIV-1 replication in resting CD4+ T lymphocytes
Pan, X., Baldauf, H., Keppler, O. T., & Fackler, O. (2013) · Cell Research · doi:10.1038/cr.2013.74 · Cited by 152
Resistance to type 1 interferons is a major determinant of HIV-1 transmission fitness
Iyer, S. S., Bibollet‐Ruche, F., Sherrill-Mix, S. A., Learn, G. H., Plenderleith, L. J., Smith, A. G., Barbian, H. J., Russell, R. M., Gondim, M. V. P., Bahari, C. Y., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1620144114 · Cited by 145
Structural basis of cellular dNTP regulation by SAMHD1
Ji, X., Tang, C., Zhao, Q., Wang, W., & Xiong, Y. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1412289111 · Cited by 143
Restriction of diverse retroviruses by SAMHD1
Gramberg, T., Kahle, T., Bloch, N., Wittmann, S., Müllers, E., Daddacha, W. B., Hofmann, H., Kim, B., Lindemann, D., & Landau, N. R. (2013) · Retrovirology · doi:10.1186/1742-4690-10-26 · Cited by 150
“HIV-1 does not encode Vpx and its Vpr does not counteract SAMHD1 [1].”
InfluentialContribution of SAM and HD domains to retroviral restriction mediated by human SAMHD1
White, T. E., Brandariz-Núñez, A., Valle‐Casuso, J. C., Amie, S. M., Nguyen, L. A., Kim, B., Brojatsch, J., & Diaz‐Griffero, F. (2012) · Virology · doi:10.1016/j.virol.2012.10.029 · Cited by 148
“Recent work identified SAMHD1 as the protein that blocks infection of SIVDVpx, HIV-2DVpx and HIV-1 before reverse transcription in macrophages and dendritic cells (Hrecka et al., 2011; Laguette et al., 2011).”
HIV-2/SIV viral protein X counteracts HUSH repressor complex
Chougui, G., Munir, S., Matkovic, R., Martin, M. M., Morel, M., Lahouassa, H., Leduc, M., Ramírez, B. C., Etienne, L., & Margottin-Goguet, F. (2018) · Nature Microbiology · doi:10.1038/s41564-018-0179-6 · Cited by 146
Cyclophilin A protects HIV-1 from restriction by human TRIM5α
Kim, K., Dauphin, A., Keceli, S. K., McCauley, S. M., Yurkovetskiy, L., Carbone, C., Diehl, W. E., Strambio‐De‐Castillia, C., Campbell, E. M., & Luban, J. (2019) · Nature Microbiology · doi:10.1038/s41564-019-0592-5 · Cited by 137
The Vpx Lentiviral Accessory Protein Targets SAMHD1 for Degradation in the Nucleus
Hofmann, H., Logue, E. C., Bloch, N., Daddacha, W. B., Polsky, S. B., Schultz, M. L., Kim, B., & Landau, N. R. (2012) · Journal of Virology · doi:10.1128/jvi.01657-12 · Cited by 150
“The pretreatment of DC with Vpx-containing VLPs enhances vpx SIV and HIV-1 infections by as much as 100-fold (7, 14, 18, 26).”
BackgroundGonçalves, A., Karayel, E., Rice, G., Bennett, K. L., Crow, Y. J., Superti‐Furga, G., & Bürckstümmer, T. (2012) · Human Mutation · doi:10.1002/humu.22087 · Cited by 143
“HIV-2, in contrast, is not restricted as it harbors the Vpx protein, which antagonizes SAMHD1 by recruiting an E3 ligase complex and triggering the proteasomal degradation of SAMHD1.”
BackgroundHIV accessory proteins versus host restriction factors
Strebel, K. (2013) · Current Opinion in Virology · doi:10.1016/j.coviro.2013.08.004 · Cited by 152
Structural basis of lentiviral subversion of a cellular protein degradation pathway
Schwefel, D., Groom, H. C. T., Boucherit, V., Christodoulou, E., Walker, P. A., Stoye, J. P., Bishop, K. N., & Taylor, I. A. (2013) · Nature · doi:10.1038/nature12815 · Cited by 133
Pauls, E., Ruiz, A., Badía, R., Permanyer, M., Gubern, A., Riveira‐Muñoz, E., Torres‐Torronteras, J., Álvarez, M., Mothe, B., Brander, C., et al. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1400873 · Cited by 136
“pool and eliminating the cellular restriction to lentiviral RT (10).”
BackgroundSAMHD1 Restricts Herpes Simplex Virus 1 in Macrophages by Limiting DNA Replication
Kim, E. T., White, T. E., Brandariz-Núñez, A., Diaz‐Griffero, F., & Weitzman, M. D. (2013) · Journal of Virology · doi:10.1128/jvi.02291-13 · Cited by 127
“It was identified through biochemical purification of the accessory factor Vpx encoded by certain lentiviruses (8, 9).”
BackgroundInfluentialIzquierdo‐Useros, N., Lorizate, M., McLaren, P. J., Telenti, A., Kräusslich, H., & Martínez‐Picado, J. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1004146 · Cited by 135
“In contrast to HIV-1, HIV-2 naturally infects DCs [20], and this function depends on counteraction of SAMHD1 by Vpx, a viral protein not present in HIV-1 [17,18].”
Background
Metadata
- Authors
- Hrecka, K., Hao, C., Gierszewska, M., Swanson, S. K., Kesik-Brodacka, M., Srivastava, S., Florens, L., Washburn, M. P., & Skowronski, J.
- Affiliations
- Case Western Reserve University (US)
- Cold Spring Harbor Laboratory (US)
- Stowers Institute for Medical Research (US)
- Venue
- Nature
- Published
- 2011-06
- Volume
- 474
- Issue
- 7353
- Pages
- 658-661
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3179858
- OpenAlex
- W1964567249
- Cited by
- 1,200
- References
- 30
- Citations by year
- 2026: 30 · 2025: 51 · 2024: 54 · 2023: 47 · 2022: 62 · 2021: 58 · 2020: 66 · 2019: 82 · 2018: 88 · 2017: 87 · 2016: 91 · 2015: 101 · 2014: 125 · 2013: 125 · 2012: 109
- FWCI
- 48.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R21AI084694, R01AI077459)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- HIV-1, Vpx, SAMHD1, macrophages, dendritic cells, host restriction factors, proteasomal degradation, Aicardi-Goutières syndrome, innate immunity, interferon response, retroviral infection, HIV-2, simian immunodeficiency virus
- MeSH terms
- SAM Domain and HD Domain-Containing Protein 1, Carrier Proteins, Cells, Cultured, Humans, Macrophages, Nuclear Proteins, HIV-1, HIV Infections, Protein Serine-Threonine Kinases, Monomeric GTP-Binding Proteins, Ubiquitin-Protein Ligases, Proteasome Endopeptidase Complex, Viral Regulatory and Accessory Proteins, HEK293 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
