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Cited by 146interferon and immune responsesSARS-CoV-2 and COVID-19 ResearchAnimal Virus Infections Studies

SARS-CoV-2 Is Restricted by Zinc Finger Antiviral Protein despite Preadaptation to the Low-CpG Environment in Humans

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Nchioua, Rayhane, Kmiec, Dorota, Müller, Janis A., Conzelmann, Carina, Groß, Rüdiger, Swanson, Chad M., Neil, Stuart J. D., Stenger, Steffen +4 more·2020·mBio
DOI 10.1128/mbio.01930-20PMC PMC7569149

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Abstract

Although interferons inhibit SARS-CoV-2 and have been evaluated for treatment of coronavirus disease 2019 (COVID-19), the most effective types and antiviral effectors remain to be defined. Here, we show that IFN-γ is particularly potent in restricting SARS-CoV-2 and in inducing expression of the antiviral factor ZAP in human lung cells. Knockdown experiments revealed that endogenous ZAP significantly restricts SARS-CoV-2. We further show that CpG dinucleotides which are specifically targeted by ZAP are strongly suppressed in the SARS-CoV-2 genome and that the two closest horseshoe bat relatives of SARS-CoV-2 show the lowest genomic CpG content of all coronavirus sequences available from this reservoir host. Nonetheless, both the short and long isoforms of human ZAP reduced SARS-CoV-2 RNA levels, and this activity was conserved in horseshoe bat and pangolin ZAP orthologues. Our findings indicating that type II interferon is particularly efficient against SARS-CoV-2 and that ZAP restricts this pandemic viral pathogen might promote the development of effective immune therapies against COVID-19.

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  • Host zinc finger antiviral proteins (ZAP, gene name ZC3HAV1) target CpG dinucleotides in viral RNA and recruit cellular RNA degradation complexes to degrade the viral RNA genome.

    “This avoidance of CGN codons makes evolutionary sense given that the host zinc finger antiviral proteins (ZAP, gene name ZC3HAV1) target CpG dinucleotides in viral RNA and recruit cellular RNA degradation complexes to degrade the viral RNA genome [27,28,29].”

    From Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines (2021) · cites this paper as [29]

    The Introduction says ZAP targets CpG-rich viral RNA, and the Results section on ZAP isoforms says it promotes degradation of CpG-containing viral RNAs. Another Results section notes that ZAP lacks RNase activity and identifies cellular cofactors important for restriction, but our copy does not establish that ZAP recruits RNA-degradation complexes to degrade the viral genome. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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  1. [1]Zhou P, Yang X-L, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang R-D, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL 2020 A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579: 270– 273. doi: 10.1038/s41586-020-2012-7. 32015507 PMC7095418 · DOI · Paper page
  2. [2]Zheng Z, Peng F, Xu B, Zhao J, Liu H, Peng J, Li Q, Jiang C, Zhou Y, Liu S, Ye C, Zhang P, Xing Y, Guo H, Tang W 2020 Risk factors of critical & mortal COVID-19 cases: a systematic literature review and meta-analysis. J Infect 81: E16– E25. doi: 10.1016/j.jinf.2020.04.021. PMC7177098 32335169 · DOI · Paper page
  3. [3]Graham RL, Baric RS 2010 Recombination, reservoirs, and the modular spike: mechanisms of coronavirus cross-species transmission. J Virol 84: 3134– 3146. doi: 10.1128/JVI.01394-09. 19906932 PMC2838128 · DOI
  4. [4]Petrosillo N, Viceconte G, Ergonul O, Ippolito G, Petersen E 2020 COVID-19, SARS and MERS: are they closely related? Clin Microbiol Infect 26: 729– 734. doi: 10.1016/j.cmi.2020.03.026. 32234451 PMC7176926 · DOI
  5. [5]Mantlo E, Bukreyeva N, Maruyama J, Paessler S, Huang C 2020 Antiviral activities of type I interferons to SARS-CoV-2 infection. Antiviral Res 179: 104811. doi: 10.1016/j.antiviral.2020.104811. 32360182 PMC7188648 · DOI
  6. [6]Sallard E, Lescure FX, Yazdanpanah Y, Mentre F, Peiffer-Smadja N 2020 Type 1 interferons as a potential treatment against COVID-19. Antiviral Res 178: 104791. doi: 10.1016/j.antiviral.2020.104791. 32275914 PMC7138382 · DOI
  7. [7]Woo PCY, Wong BHL, Huang Y, Lau SKP, Yuen KY 2007 Cytosine deamination and selection of CpG suppressed clones are the two major independent biological forces that shape codon usage bias in coronaviruses. Virology 369: 431– 442. doi: 10.1016/j.virol.2007.08.010. 17881030 PMC7103290 · DOI
  8. [8]Xia X 2020 Extreme genomic CpG deficiency in SARS-CoV-2 and evasion of host antiviral defense. Mol Biol Evol 37: 2699– 2705. doi: 10.1093/molbev/msaa094. 32289821 PMC7184484 · DOI · Paper page
  9. [9]Ghimire D, Rai M, Gaur R 2018 Novel host restriction factors implicated in HIV-1 replication. J Gen Virol 99: 435– 446. doi: 10.1099/jgv.0.001026. 29465030 · DOI
  10. [10]Takata MA, Gonçalves-Carneiro D, Zang TM, Soll SJ, York A, Blanco-Melo D, Bieniasz PD 2017 CG dinucleotide suppression enables antiviral defence targeting non-self RNA. Nature 550: 124– 127. doi: 10.1038/nature24039. 28953888 PMC6592701 · DOI · Paper page
  11. [11]Cui J, Li F, Shi ZL 2019 Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol 17: 181– 192. doi: 10.1038/s41579-018-0118-9. 30531947 PMC7097006 · DOI
  12. [12]Corman VM, Muth D, Niemeyer D, Drosten C 2018 Hosts and sources of endemic human coronaviruses. Adv Virus Res 100: 163– 188. doi: 10.1016/bs.aivir.2018.01.001. 29551135 PMC7112090 · DOI
  13. [13]Banerjee A, Kulcsar K, Misra V, Frieman M, Mossman K 2019 Bats and coronaviruses. Viruses 11: 41. doi: 10.3390/v11010041. PMC6356540 30634396 · DOI
  14. [14]Van Der Hoek L, Pyrc K, Jebbink MF, Vermeulen-Oost W, Berkhout RJM, Wolthers KC, Wertheim-Van Dillen PME, Kaandorp J, Spaargaren J, Berkhout B 2004 Identification of a new human coronavirus. Nat Med 10: 368– 373. doi: 10.1038/nm1024. 15034574 PMC7095789 · DOI
  15. [15]Woo PCY, Lau SKP, Yip CCY, Huang Y, Tsoi H-W, Chan K-H, Yuen K-Y 2006 Comparative analysis of 22 coronavirus HKU1 genomes reveals a novel genotype and evidence of natural recombination in coronavirus HKU1. J Virol 80: 7136– 7145. doi: 10.1128/JVI.00509-06. 16809319 PMC1489027 · DOI
  16. [16]Ksiazek TG, Erdman D, Goldsmith CS, Zaki SR, Peret T, Emery S, Tong S, Urbani C, Comer JA, Lim W, Rollin PE, Dowell SF, Ling A-E, Humphrey CD, Shieh W-J, Guarner J, Paddock CD, Rota P, Fields B, DeRisi J, Yang J-Y, Cox N, Hughes JM, LeDuc JW, Bellini WJ, Anderson LJ, SARS Working Group. 2003 A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med 348: 1953– 1966. doi: 10.1056/NEJMoa030781. 12690092 · DOI
  17. [17]Bermingham A, Chand MA, Brown CS, Aarons E, Tong C, Langrish C, Hoschler K, Brown K, Galiano M, Myers R, Pebody RG, Green HK, Boddington NL, Gopal R, Price N, Newsholme W, Drosten C, Fouchier RA, Zambon M 2012 Severe respiratory illness caused by a novel coronavirus, in a patient transferred to the United Kingdom from the Middle East, September 2012. Eurosurveillance 17: 20290. doi: 10.2807/ese.17.40.20290-en. 23078800 · DOI
  18. [18]Zhou H, Chen X, Hu T, Li J, Song H, Liu Y, Wang P, Liu D, Yang J, Holmes EC, Hughes AC, Bi Y, Shi W 2020 A novel bat coronavirus closely related to SARS-CoV-2 contains natural insertions at the S1/S2 cleavage site of the spike protein. Curr Biol 30: 2196– 2203.e3. doi: 10.1016/j.cub.2020.05.023. 32416074 PMC7211627 · DOI
  19. [19]Xiao K, Zhai J, Feng Y, Zhou N, Zhang X, Zou J-J, Li N, Guo Y, Li X, Shen X, Zhang Z, Shu F, Huang W, Li Y, Zhang Z, Chen R-A, Wu Y-J, Peng S-M, Huang M, Xie W-J, Cai Q-H, Hou F-H, Chen W, Xiao L, Shen Y 2020 Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins. Nature 583: 286– 289. doi: 10.1038/s41586-020-2313-x. 32380510 · DOI · Paper page
  20. [20]Lam TT-Y, Jia N, Zhang Y-W, Shum MH-H, Jiang J-F, Zhu H-C, Tong Y-G, Shi Y-X, Ni X-B, Liao Y-S, Li W-J, Jiang B-G, Wei W, Yuan T-T, Zheng K, Cui X-M, Li J, Pei G-Q, Qiang X, Cheung WY-M, Li L-F, Sun F-F, Qin S, Huang J-C, Leung GM, Holmes EC, Hu Y-L, Guan Y, Cao W-C 2020 Identifying SARS-CoV-2 related coronaviruses in Malayan pangolins. Nature 583: 282– 285. doi: 10.1038/s41586-020-2169-0. 32218527 · DOI
  21. [21]MacLean OA, Lytras S, Singer JB, Weaver S, Pond SLK, Robertson DL 2020 Evidence of significant natural selection in the evolution of SARS-CoV-2 in bats, not humans. bioRxiv doi: 10.1101/2020.05.28.122366. · DOI
  22. [22]Digard P, Lee HM, Sharp C, Grey F, Gaunt E 2020 Intra-genome variability in the dinucleotide composition of SARS-CoV-2. Virus Evol doi: 10.1093/ve/veaa057. PMC7454914 33029383 · DOI
  23. [23]Dominguez SR, Sims GE, Wentworth DE, Halpin RA, Robinson CC, Town CD, Holmes KV 2012 Genomic analysis of 16 Colorado human NL63 coronaviruses identifies a new genotype, high sequence diversity in the N-terminal domain of the spike gene and evidence of recombination. J Gen Virol 93: 2387– 2398. doi: 10.1099/vir.0.044628-0. 22837419 PMC4091283 · DOI
  24. [24]Ye ZW, Yuan S, Yuen KS, Fung SY, Chan CP, Jin DY 2020 Zoonotic origins of human coronaviruses. Int J Biol Sci 16: 1686– 1697. doi: 10.7150/ijbs.45472. 32226286 PMC7098031 · DOI
  25. [25]Greenbaum BD, Levine AJ, Bhanot G, Rabadan R 2008 Patterns of evolution and host gene mimicry in influenza and other RNA viruses. PLoS Pathog 4: e1000079. doi: 10.1371/journal.ppat.1000079. 18535658 PMC2390760 · DOI
  26. [26]Deaton AM, Bird A 2011 CpG islands and the regulation of transcription. Genes Dev 25: 1010– 1022. doi: 10.1101/gad.2037511. 21576262 PMC3093116 · DOI · Paper page
  27. [27]Saxonov S, Berg P, Brutlag DL 2006 A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proc Natl Acad Sci U S A 103: 1412– 1417. doi: 10.1073/pnas.0510310103. 16432200 PMC1345710 · DOI · Paper page
  28. [29]Odon V, Fros JJ, Goonawardane N, Dietrich I, Ibrahim A, Alshaikhahmed K, Nguyen D, Simmonds P 2019 The role of ZAP and OAS3/RNAseL pathways in the attenuation of an RNA virus with elevated frequencies of CpG and UpA dinucleotides. Nucleic Acids Res 47: 8061– 8083. doi: 10.1093/nar/gkz581. 31276592 PMC6735852 · DOI
  29. [30]Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu N-H, Nitsche A, Müller MA, Drosten C, Pöhlmann S 2020 SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181: 271– 280.e8. doi: 10.1016/j.cell.2020.02.052. 32142651 PMC7102627 · DOI · Paper page
  30. [31]Matsuyama S, Nao N, Shirato K, Kawase M, Saito S, Takayama I, Nagata N, Sekizuka T, Katoh H, Kato F, Sakata M, Tahara M, Kutsuna S, Ohmagari N, Kuroda M, Suzuki T, Kageyama T, Takeda M 2020 Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. Proc Natl Acad Sci U S A 117: 7001– 7003. doi: 10.1073/pnas.2002589117. 32165541 PMC7132130 · DOI
  31. [32]Li MMH, Lau Z, Cheung P, Aguilar EG, Schneider WM, Bozzacco L, Molina H, Buehler E, Takaoka A, Rice CM, Felsenfeld DP, MacDonald MR 2017 TRIM25 enhances the antiviral action of zinc-finger antiviral protein (ZAP). PLoS Pathog 13: e1006145. doi: 10.1371/journal.ppat.1006145. 28060952 PMC5245905 · DOI
  32. [33]Zheng X, Wang X, Tu F, Wang Q, Fan Z, Gao G 2017 TRIM25 is required for the antiviral activity of zinc finger antiviral protein. J Virol 91: e00088-17. doi: 10.1128/JVI.00088-17. 28202764 PMC5391446 · DOI
  33. [35]Park A, Iwasaki A 2020 Type I and type III interferons - induction, signaling, evasion, and application to combat COVID-19. Cell Host Microbe 27: 870– 878. doi: 10.1016/j.chom.2020.05.008. 32464097 PMC7255347 · DOI · Paper page
  34. [36]Chu H, Chan JF-W, Yuen TT-T, Shuai H, Yuan S, Wang Y, Hu B, Yip CC-Y, Tsang JO-L, Huang X, Chai Y, Yang D, Hou Y, Chik KK-H, Zhang X, Fung AY-F, Tsoi H-W, Cai J-P, Chan W-M, Ip JD, Chu AW-H, Zhou J, Lung DC, Kok K-H, To KK-W, Tsang OT-Y, Chan K-H, Yuen K-Y 2020 Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: an observational study. Lancet Microbe 1: e14– e23. doi: 10.1016/S2666-5247(20)30004-5. 32835326 PMC7173822 · DOI
  35. [37]Blanco-Melo D, Nilsson-Payant BE, Liu W-C, Uhl S, Hoagland D, Møller R, Jordan TX, Oishi K, Panis M, Sachs D, Wang TT, Schwartz RE, Lim JK, Albrecht RA, Tenoever BR 2020 Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell 181: 1036– 1045.e9. doi: 10.1016/j.cell.2020.04.026. 32416070 PMC7227586 · DOI · Paper page
  36. [38]Li MMH, Aguilar EG, Michailidis E, Pabon J, Park P, Wu X, de Jong YP, Schneider WM, Molina H, Rice CM, MacDonald MR 2019 Characterization of novel splice variants of zinc finger antiviral protein (ZAP). J Virol 93: e00715-19. doi: 10.1128/JVI.00715-19. 31118263 PMC6714797 · DOI
  37. [39]Charron G, Li MMH, MacDonald MR, Hang HC 2013 Prenylome profiling reveals S-farnesylation is crucial for membrane targeting and antiviral activity of ZAP long-isoform. Proc Natl Acad Sci U S A 110: 11085– 11090. doi: 10.1073/pnas.1302564110. 23776219 PMC3703996 · DOI
  38. [40]Schwerk J, Soveg FW, Ryan AP, Thomas KR, Hatfield LD, Ozarkar S, Forero A, Kell AM, Roby JA, So L, Hyde JL, Gale M, Daugherty MD, Savan R 2019 RNA-binding protein isoforms ZAP-S and ZAP-L have distinct antiviral and immune resolution functions. Nat Immunol 20: 1610– 1620. doi: 10.1038/s41590-019-0527-6. 31740798 PMC7240801 · DOI
  39. [41]Hayakawa S, Shiratori S, Yamato H, Kameyama T, Kitatsuji C, Kashigi F, Goto S, Kameoka S, Fujikura D, Yamada T, Mizutani T, Kazumata M, Sato M, Tanaka J, Asaka M, Ohba Y, Miyazaki T, Imamura M, Takaoka A 2011 ZAPS is a potent stimulator of signaling mediated by the RNA helicase RIG-I during antiviral responses. Nat Immunol 12: 37– 44. doi: 10.1038/ni.1963. 21102435 · DOI
  40. [42]Zhang B, Goraya MU, Chen N, Xu L, Hong Y, Zhu M, Chen J-L 2020 Zinc finger CCCH-type antiviral protein 1 restricts the viral replication by positively regulating type I interferon response. Front Microbiol 11: 1912. doi: 10.3389/fmicb.2020.01912. 32922375 PMC7456897 · DOI
  41. [43]Meagher JL, Takata M, Gonçalves-Carneiro D, Keane SC, Rebendenne A, Ong H, Orr VK, MacDonald MR, Stuckey JA, Bieniasz PD, Smith JL 2019 Structure of the zinc-finger antiviral protein in complex with RNA reveals a mechanism for selective targeting of CG-rich viral sequences. Proc Natl Acad Sci U S A 116: 24303– 24309. doi: 10.1073/pnas.1913232116. 31719195 PMC6883784 · DOI
  42. [44]Luo X, Wang X, Gao Y, Zhu J, Liu S, Gao G, Gao P 2020 Molecular mechanism of RNA recognition by zinc-finger antiviral protein. Cell Rep 30: 46– 52.e4. doi: 10.1016/j.celrep.2019.11.116. 31914396 · DOI
  43. [45]Kim D, Lee JY, Yang JS, Kim JW, Kim VN, Chang H 2020 The architecture of SARS-CoV-2 transcriptome. Cell 181: 914– 921.e10. doi: 10.1016/j.cell.2020.04.011. 32330414 PMC7179501 · DOI · Paper page
  44. [46]Di Gioacchino A, Sulc P, Komarova AV, Greenbaum BD, Monasson R, Cocco S 2020 The heterogeneous landscape and early evolution of pathogen-associated CpG dinucleotides in SARS-CoV-2. bioRxiv doi: 10.1101/2020.05.06.074039. PMC7928797 33555346 · DOI
  45. [47]Kmiec D, Nchioua R, Sherrill-Mix S, Stürzel CM, Heusinger E, Braun E, Gondim MVP, Hotter D, Sparrer KMJ, Hahn BH, Sauter D, Kirchhoff F 2020 CpG frequency in the 5’ third of the env gene determines sensitivity of primary HIV-1 strains to the zinc-finger antiviral protein. mBio 11: e02903-19. doi: 10.1128/mBio.02903-19. 31937644 PMC6960287 · DOI
  46. [48]Tse LV, Hamilton AM, Friling T, Whittaker GR 2014 A novel activation mechanism of avian influenza virus H9N2 by furin. J Virol 88: 1673– 1683. doi: 10.1128/JVI.02648-13. 24257604 PMC3911587 · DOI
  47. [50]Coutard B, Valle C, de Lamballerie X, Canard B, Seidah NG, Decroly E 2020 The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade. Antiviral Res 176: 104742. doi: 10.1016/j.antiviral.2020.104742. 32057769 PMC7114094 · DOI
  48. [51]Ogando NS, Dalebout TJ, Zevenhoven-Dobbe JC, Limpens RWAL, van der Meer Y, Caly L, Druce J, de Vries JJC, Kikkert M, Bárcena M, Sidorov I, Snijder EJ 2020 SARS-coronavirus-2 replication in Vero E6 cells: replication kinetics, rapid adaptation and cytopathology. J Gen Virol 101: 925– 940. doi: 10.1099/jgv.0.001453. 32568027 PMC7654748 · DOI
  49. [52]Andres C, Garcia-Cehic D, Gregori J, Piñana M, Rodriguez-Frias F, Guerrero-Murillo M, Esperalba J, Rando A, Goterris L, Codina MG, Quer S, Martín MC, Campins M, Ferrer R, Almirante B, Esteban JI, Pumarola T, Antón A, Quer J 2020 Naturally occurring SARS-CoV-2 gene deletions close to the spike S1/S2 cleavage site in the viral quasispecies of COVID19 patients. Emerging Microbes Infect 9: 1900– 1911. doi: 10.1101/2020.06.03.129585. PMC8284971 32752979 · DOI
  50. [53]Gu H, Chu DKW, Peiris M, Poon LLM 2020 Multivariate analyses of codon usage of SARS-CoV-2 and other betacoronaviruses. Virus Evol 6: veaa032. doi: 10.1093/ve/veaa032. 32431949 PMC7223271 · DOI
  51. [55]Stanifer ML, Kee C, Cortese M, Zumaran CM, Triana S, Mukenhirn M, Kraeusslich HG, Alexandrov T, Bartenschlager R, Boulant S 2020 Critical role of type III interferon in controlling SARS-CoV-2 infection in human intestinal epithelial cells. Cell Rep 32: 107863. doi: 10.1016/j.celrep.2020.107863. 32610043 PMC7303637 · DOI
  52. [56]Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, Wang T, Zhang X, Chen H, Yu H, Zhang X, Zhang M, Wu S, Song J, Chen T, Han M, Li S, Luo X, Zhao J, Ning Q 2020 Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest 130: 2620– 2629. doi: 10.1172/JCI137244. 32217835 PMC7190990 · DOI · Paper page
  53. [57]Zheng HY, Zhang M, Yang CX, Zhang N, Wang XC, Yang XP, Dong XQ, Zheng YT 2020 Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients. Cell Mol Immunol 17: 541– 543. doi: 10.1038/s41423-020-0401-3. 32203186 PMC7091621 · DOI · Paper page
  54. [58]Ni L, Cheng M-L, Zhao H, Feng Y, Liu J, Ye F, Ye Q, Zhu G, Li X, Wang P, Shao J, Wei P, Chen F, Qin C-F, Wang G, Li F, Zeng H, Dong C 2020 Impaired cellular immunity to SARS-CoV-2 in severe COVID-19 1 patients. medRxiv doi: 10.1101/2020.08.10.20171371. PMC7884325 33603759 · DOI
  55. [59]Totura AL, Baric RS 2012 SARS coronavirus pathogenesis: host innate immune responses and viral antagonism of interferon. Curr Opin Virol 2: 264– 275. doi: 10.1016/j.coviro.2012.04.004. 22572391 PMC7102726 · DOI
  56. [60]Fehr AR, Perlman S 2015 Coronaviruses: an overview of their replication and pathogenesis Methods Mol Biol 2182: 1– 23. doi: 10.1007/978-1-4939-2438-7_1. PMC4369385 25720466 · DOI
  57. [61]Thoms M, Buschauer R, Ameismeier M, Koepke L, Denk T, Hirschenberger M, Kratzat H, Hayn M, Mackens-Kiani T, Cheng J, Straub JH, Stürzel CM, Fröhlich T, Berninghausen O, Becker T, Kirchhoff F, Sparrer KMJ, Beckmann R 2020 Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2. Science 369: eabc8665. doi: 10.1126/science.abc8665. PMC7402621 32680882 · DOI
  58. [62]Koehorst J, van Dam JCJ, Saccenti E, Martins dos Santos VAP 2017 GISAID: global initiative on sharing all influenza data – from vision to reality. Euro Surveill 22(13):pii=30494. https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2017.22.13.30494. PMC5388101 28382917 · DOI · Paper page
  59. [63]Sievers F, Wilm A, Dineen D, Gibson TJ, Karplus K, Li W, Lopez R, McWilliam H, Remmert M, Söding J, Thompson JD, Higgins DG 2011 Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol 7: 539. doi: 10.1038/msb.2011.75. 21988835 PMC3261699 · DOI
  60. [64]Lemoine F, Correia D, Lefort V, Doppelt-Azeroual O, Mareuil F, Cohen-Boulakia S, Gascuel O 2019 NGPhylogeny.fr: new generation phylogenetic services for non-specialists. Nucleic Acids Res 47: W263– W265. doi: 10.1093/nar/gkz303. PMC6602494 31028399 · DOI
  61. [65]Letunic I, Bork P 2019 Interactive Tree of Life (iTOL) v4: recent updates and new developments. Nucleic Acids Res 47: W256– W259. doi: 10.1093/nar/gkz239. 30931475 PMC6602468 · DOI
  62. [66]Groß R, Conzelmann C, Müller JA, Stenger S, Steinhart K, Kirchhoff F, Münch J 2020 Detection of SARS-CoV-2 in human breastmilk. Lancet 395: 1757– 1758. doi: 10.1016/S0140-6736(20)31181-8. 32446324 PMC7241971 · DOI
  63. [67]Reed LJ, Muench H 1938 A simple method of estimating fifty per cent endpoints. Am J Epidemiol 27: 493– 497. doi: 10.1093/oxfordjournals.aje.a118408. · DOI

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Authors
Nchioua, R., Kmiec, D., Müller, J. A., Conzelmann, C., Groß, R., Swanson, C. M., Neil, S. J. D., Stenger, S., Sauter, D., Münch, J., Sparrer, K. M. J., & Kirchhoff, F.
Affiliations
  • University Hospital Ulm (DE)
  • Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany
  • King's College London (GB)
Corresponding author
Kirchhoff, Frank
ORCID
Venue
mBio
Publisher
American Society for Microbiology
Published
2020-10-27
Volume
11
Issue
5
ISSN
  • 2150-7511 (ISSN-L)
  • 2161-2129
DOI
10.1128/mbio.01930-20
PMC
PMC7569149
OpenAlex
W3093413235
Cited by
146
References
4
Citations by year
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9.88
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journal article
Language
en
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Funders
  • Deutsche Forschungsgemeinschaft (CRC-1279, SPP-1923, SP 1600/4-1, KM 5/1-1, SP1600)
  • Bundesministerium für Bildung und Forschung (KM 5/1-1, SPP 1923, SARS-CoV-2, CRC1279, RestrictSARS-CoV2)
  • Universität Ulm (CRC 1279, SP1600)
  • Medical Research Council (MC_PC_14105, MR/S000844/1, MC_PC_15068)
  • International Graduate School in Molecular Medicine Ulm (SARS-CoV-2)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
Keywords
SARS-CoV-2, zinc-finger antiviral protein, ZAP, interferon-gamma, CpG, antiviral restriction, horseshoe bats, pangolins, viral genome evolution, COVID-19 pandemic, lung cells, interferon therapy
MeSH terms
Betacoronavirus, COVID-19, SARS-CoV-2, Animals, Cell Line, Humans, Interferons, Phylogeny, Pneumonia, Viral, RNA, Viral, Virus Replication, Gene Expression, RNA-Binding Proteins, Genome, Viral, Coronavirus, Coronavirus Infections, CpG Islands, Protein Isoforms, Pandemics

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 ›

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