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Annual Review of Virology

Volume 8, 2021

Adenosine Deaminases Acting on RNA (ADARs) and Viral Infections

Abstract

C6 deamination of adenosine (A) to inosine (I) in double-stranded RNA (dsRNA) is catalyzed by a family of enzymes known as ADARs (adenosine deaminases acting on RNA) encoded by three genes in mammals. Alternative promoters and splicing produce two ADAR1 proteins, an interferon-inducible cytoplasmic p150 and a constitutively expressed p110 that like ADAR2 is a nuclear enzyme. ADAR3 lacks deaminase activity. A-to-I editing occurs with both viral and cellular RNAs. Deamination activity is dependent on dsRNA substrate structure and regulatory RNA-binding proteins and ranges from highly site selective with hepatitis D RNA and glutamate receptor precursor messenger RNA (pre-mRNA) to hyperediting of measles virus and polyomavirus transcripts and cellular inverted elements. Because I base-pairs as guanosine instead of A, editing can alter mRNA decoding, pre-mRNA splicing, and microRNA silencing. Editing also alters dsRNA structure, thereby suppressing innate immune responses including interferon production and action.

Keyword(s): ADAR, adenosine deaminase acting on RNA, autoimmunity, double-stranded RNA, dsRNA, innate immunity, interferon, RNA editing
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2021-09-29
2024-05-13
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Literature Cited

  1. 1. 
    Bass BL, Nishikura K, Keller W, Seeburg PH, Emeson RB et al. 1997. A standardized nomenclature for adenosine deaminases that act on RNA. RNA 3:947–49
     [Google Scholar]
  2. 2. 
    Bass BL, Weintraub H. 1987. A developmentally regulated activity that unwinds RNA duplexes. Cell 48:607–13
     [Google Scholar]
  3. 3. 
    Rebagliati MR, Melton DA. 1987. Antisense RNA injections in fertilized frog eggs reveal an RNA duplex unwinding activity. Cell 48:599–605
     [Google Scholar]
  4. 4. 
    Nishikura K. 2016. A-to-I editing of coding and non-coding RNAs by ADARs. Nat. Rev. Mol. Cell Biol. 17:83–96
     [Google Scholar]
  5. 5. 
    Walkley CR, Li JB. 2017. Rewriting the transcriptome: adenosine-to-inosine RNA editing by ADARs. Genome Biol 18:205
     [Google Scholar]
  6. 6. 
    Eisenberg E, Levanon EY. 2018. A-to-I RNA editing—immune protector and transcriptome diversifier. Nat. Rev. Genet. 19:473–90
     [Google Scholar]
  7. 7. 
    Samuel CE. 2019. Adenosine deaminase acting on RNA (ADAR1), a suppressor of double-stranded RNA-triggered innate immune responses. J. Biol. Chem. 294:1710–20
     [Google Scholar]
  8. 8. 
    Reich DP, Bass BL. 2019. Mapping the dsRNA world. Cold Spring Harb. Perspect. Biol. 11:a035352
     [Google Scholar]
  9. 9. 
    Strobel SA, Cech TR, Usman N, Beigelman L. 1994. The 2,6-diaminopurine riboside⋅5-methylisocytidine wobble base pair: an isoenergetic substitution for the study of G⋅U pairs in RNA. Biochemistry 33:13824–35
     [Google Scholar]
  10. 10. 
    Hershfield MS. 2003. Genotype is an important determinant of phenotype in adenosine deaminase deficiency. Curr. Opin. Immunol. 15:571–77
     [Google Scholar]
  11. 11. 
    Rice GI, Kasher PR, Forte GM, Mannion NM, Greenwood SM et al. 2012. Mutations in ADAR1 cause Aicardi-Goutières syndrome associated with a type I interferon signature. Nat. Genet. 44:1243–48
     [Google Scholar]
  12. 12. 
    Herbert A. 2020. Mendelian disease caused by variants affecting recognition of Z-DNA and Z-RNA by the Zα domain of the double-stranded RNA editing enzyme ADAR. Eur. J. Hum. Genet. 28:114–17
     [Google Scholar]
  13. 13. 
    Miyamura Y, Suzuki T, Kono M, Inagaki K, Ito S et al. 2003. Mutations of the RNA-specific adenosine deaminase gene (DSRAD) are involved in dyschromatosis symmetrica hereditaria. Am. J. Hum. Genet. 73:693–99
     [Google Scholar]
  14. 14. 
    Colby C, Duesberg PH. 1969. Double-stranded RNA in vaccinia virus infected cells. Nature 222:940–44
     [Google Scholar]
  15. 15. 
    Samuel CE. 2011. Adenosine deaminases acting on RNA (ADARs) are both antiviral and proviral. Virology 411:180–93
     [Google Scholar]
  16. 16. 
    Hur S. 2019. Double-stranded RNA sensors and modulators in innate immunity. Annu. Rev. Immunol. 37:349–75
     [Google Scholar]
  17. 17. 
    George CX, Gan Z, Liu Y, Samuel CE. 2011. Adenosine deaminases acting on RNA, RNA editing, and interferon action. J. Interferon Cytokine Res. 31:99–117
     [Google Scholar]
  18. 18. 
    Tomaselli S, Galeano F, Locatelli F, Gallo A. 2015. ADARs and the balance game between virus infection and innate immune cell response. Curr. Issues Mol. Biol. 17:37–51
     [Google Scholar]
  19. 19. 
    Lamers MM, van den Hoogen BG, Haagmans BL. 2019. ADAR1: “editor-in-chief” of cytoplasmic innate immunity. Front. Immunol. 10:1763
     [Google Scholar]
  20. 20. 
    Patterson JB, Samuel CE. 1995. Expression and regulation by interferon of a double-stranded-RNA-specific adenosine deaminase from human cells: evidence for two forms of the deaminase. Mol. Cell. Biol. 15:5376–88
     [Google Scholar]
  21. 21. 
    Weier HU, George CX, Greulich KM, Samuel CE. 1995. The interferon-inducible, double-stranded RNA-specific adenosine deaminase gene (DSRAD) maps to human chromosome 1q21.1–21.2. Genomics 30:372–75
     [Google Scholar]
  22. 22. 
    Kim U, Wang Y, Sanford T, Zeng Y, Nishikura K. 1994. Molecular cloning of cDNA for double-stranded RNA adenosine deaminase, a candidate enzyme for nuclear RNA editing. PNAS 91:11457–61
     [Google Scholar]
  23. 23. 
    O'Connell MA, Krause S, Higuchi M, Hsuan JJ, Totty NF et al. 1995. Cloning of cDNAs encoding mammalian double-stranded RNA-specific adenosine deaminase. Mol. Cell. Biol. 15:1389–97
     [Google Scholar]
  24. 24. 
    George CX, Wagner MV, Samuel CE. 2005. Expression of interferon-inducible RNA adenosine deaminase ADAR1 during pathogen infection and mouse embryo development involves tissue-selective promoter utilization and alternative splicing. J. Biol. Chem. 280:15020–28
     [Google Scholar]
  25. 25. 
    Tan MH, Li Q, Shanmugam R, Piskol R, Kohler J et al. 2017. Dynamic landscape and regulation of RNA editing in mammals. Nature 550:249–54
     [Google Scholar]
  26. 26. 
    Sun T, Yu Y, Wu X, Acevedo A, Luo J-D et al. 2021. Decoupling expression and editing preferences of ADAR1 p150 and p110 isoforms. PNAS 118:e2021757118
     [Google Scholar]
  27. 27. 
    Hood JL, Morabito MV, Martinez CR 3rd, Gilbert JA, Ferrick EA et al. 2014. Reovirus-mediated induction of ADAR1 (p150) minimally alters RNA editing patterns in discrete brain regions. Mol. Cell. Neurosci. 61:97–109
     [Google Scholar]
  28. 28. 
    George CX, Samuel CE. 1999. Human RNA-specific adenosine deaminase ADAR1 transcripts possess alternative exon 1 structures that initiate from different promoters, one constitutively active and the other interferon inducible. PNAS 96:4621–26
     [Google Scholar]
  29. 29. 
    George CX, Samuel CE. 1999. Characterization of the 5′-flanking region of the human RNA-specific adenosine deaminase ADAR1 gene and identification of an interferon-inducible ADAR1 promoter. Gene 229:203–13
     [Google Scholar]
  30. 30. 
    Kawakubo K, Samuel CE. 2000. Human RNA-specific adenosine deaminase (ADAR1) gene specifies transcripts that initiate from a constitutively active alternative promoter. Gene 258:165–72
     [Google Scholar]
  31. 31. 
    Hartner JC, Schmittwolf C, Kispert A, Müller AM, Higuchi M, Seeburg PH. 2004. Liver disintegration in the mouse embryo caused by deficiency in the RNA-editing enzyme ADAR1. J. Biol. Chem. 279:4894–902
     [Google Scholar]
  32. 32. 
    Wang Q, Miyakoda M, Yang W, Khillan J, Stachura DL et al. 2004. Stress-induced apoptosis associated with null mutation of ADAR1 RNA editing deaminase gene. J. Biol. Chem. 279:4952–61
     [Google Scholar]
  33. 33. 
    Stark GR, Darnell JE Jr. 2012. The JAK-STAT pathway at twenty. Immunity 36:503–14
     [Google Scholar]
  34. 34. 
    George CX, Das S, Samuel CE. 2008. Organization of the mouse RNA-specific adenosine deaminase Adar1 gene 5′-region and demonstration of STAT1-independent, STAT2-dependent transcriptional activation by interferon. Virology 380:338–43
     [Google Scholar]
  35. 35. 
    George CX, Samuel CE. 2015. STAT2-dependent induction of RNA adenosine deaminase ADAR1 by type I interferon differs between mouse and human cells in the requirement for STAT1. Virology 485:363–70
     [Google Scholar]
  36. 36. 
    Herbert A. 2019. Z-DNA and Z-RNA in human disease. Commun. Biol. 2:7
     [Google Scholar]
  37. 37. 
    Nichols PJ, Bevers S, Henen M, Kieft JS, Vicens Q, Vogeli B. 2021. Recognition of non-CpG repeats in Alu and ribosomal RNAs by the Z-RNA binding domain of ADAR1 induces A-Z junctions. Nat. Commun. 12:793
     [Google Scholar]
  38. 38. 
    Liu Y, Samuel CE. 1996. Mechanism of interferon action: functionally distinct RNA-binding and catalytic domains in the interferon-inducible, double-stranded RNA-specific adenosine deaminase. J. Virol. 70:1961–68
     [Google Scholar]
  39. 39. 
    Desterro JM, Keegan LP, Jaffray E, Hay RT, O'Connell MA, Carmo-Fonseca M. 2005. SUMO-1 modification alters ADAR1 editing activity. Mol. Biol. Cell 16:5115–26
     [Google Scholar]
  40. 40. 
    Bavelloni A, Focaccia E, Piazzi M, Raffini M, Cesarini V et al. 2019. AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and -2 inhibits deaminase activity. FASEB J 33:9044–61
     [Google Scholar]
  41. 41. 
    Sakurai M, Shiromoto Y, Ota H, Song C, Kossenkov AV et al. 2017. ADAR1 controls apoptosis of stressed cells by inhibiting Staufen1-mediated mRNA decay. Nat. Struct. Mol. Biol. 24:534–43
     [Google Scholar]
  42. 42. 
    Schade M, Turner CJ, Kühne R, Schmieder P, Lowenhaupt K et al. 1999. The solution structure of the Zα domain of the human RNA editing enzyme ADAR1 reveals a prepositioned binding surface for Z-DNA. PNAS 96:12465–70
     [Google Scholar]
  43. 43. 
    Pfaller CK, Donohue RC, Nersisyan S, Brodsky L, Cattaneo R. 2018. Extensive editing of cellular and viral double-stranded RNA structures accounts for innate immunity suppression and the proviral activity of ADAR1p150. PLOS Biol 16:e2006577
     [Google Scholar]
  44. 44. 
    Wang Y, Park S, Beal PA. 2018. Selective recognition of RNA substrates by ADAR deaminase domains. Biochemistry 57:1640–51
     [Google Scholar]
  45. 45. 
    Liu Y, Lei M, Samuel CE 2000. Chimeric double-stranded RNA-specific adenosine deaminase ADAR1 proteins reveal functional selectivity of double-stranded RNA-binding domains from ADAR1 and protein kinase PKR. PNAS 97:12541–46
     [Google Scholar]
  46. 46. 
    Hartner JC, Walkley CR, Lu J, Orkin SH. 2009. ADAR1 is essential for the maintenance of hematopoiesis and suppression of interferon signaling. Nat. Immunol. 10:109–15
     [Google Scholar]
  47. 47. 
    Ward SV, George CX, Welch MJ, Liou LY, Hahm B et al. 2011. RNA editing enzyme adenosine deaminase is a restriction factor for controlling measles virus replication that also is required for embryogenesis. PNAS 108:331–36
     [Google Scholar]
  48. 48. 
    Liddicoat BJ, Piskol R, Chalk AM, Ramaswami G, Higuchi M et al. 2015. RNA editing by ADAR1 prevents MDA5 sensing of endogenous dsRNA as nonself. Science 349:1115–20
     [Google Scholar]
  49. 49. 
    Mannion NM, Greenwood SM, Young R, Cox S, Brindle J et al. 2014. The RNA-editing enzyme ADAR1 controls innate immune responses to RNA. Cell Rep 9:1482–94
     [Google Scholar]
  50. 50. 
    Pestal K, Funk CC, Snyder JM, Price ND, Treuting PM, Stetson DB. 2015. Isoforms of RNA-editing enzyme ADAR1 independently control nucleic acid sensor MDA5-driven autoimmunity and multi-organ development. Immunity 43:933–44
     [Google Scholar]
  51. 51. 
    Bajad P, Ebner F, Amman F, Szabó B, Kapoor U et al. 2020. An internal deletion of ADAR rescued by MAVS deficiency leads to a minute phenotype. Nucleic Acids Res 48:3286–303
     [Google Scholar]
  52. 52. 
    Gerber A, O'Connell MA, Keller W. 1997. Two forms of human double-stranded RNA-specific editase 1 (hRED1) generated by the insertion of an Alu cassette. RNA 3:453–63
     [Google Scholar]
  53. 53. 
    George CX, Ramaswami G, Li JB, Samuel CE. 2016. Editing of cellular self-RNAs by adenosine deaminase ADAR1 suppresses innate immune stress responses. J. Biol. Chem. 291:6158–68
     [Google Scholar]
  54. 54. 
    Shelton PM, Duran A, Nakanishi Y, Reina-Campos M, Kasashima H et al. 2018. The secretion of miR-200s by a PKCζ/ADAR2 signaling axis promotes liver metastasis in colorectal cancer. Cell Rep 23:1178–91
     [Google Scholar]
  55. 55. 
    Higuchi M, Maas S, Single FN, Hartner J, Rozov A et al. 2000. Point mutation in an AMPA receptor gene rescues lethality in mice deficient in the RNA-editing enzyme ADAR2. Nature 406:78–81
     [Google Scholar]
  56. 56. 
    Horsch M, Seeburg PH, Adler T, Aguilar-Pimentel JA, Becker L et al. 2011. Requirement of the RNA-editing enzyme ADAR2 for normal physiology in mice. J. Biol. Chem. 286:18614–22
     [Google Scholar]
  57. 57. 
    Dawson TR, Sansam CL, Emeson RB. 2004. Structure and sequence determinants required for the RNA editing of ADAR2 substrates. J. Biol. Chem. 279:4941–51
     [Google Scholar]
  58. 58. 
    Kapoor U, Licht K, Amman F, Jakobi T, Martin D et al. 2020. ADAR-deficiency perturbs the global splicing landscape in mouse tissues. Genome Res 30:1107–18
     [Google Scholar]
  59. 59. 
    Chen CX, Cho DS, Wang Q, Lai F, Carter KC, Nishikura K. 2000. A third member of the RNA-specific adenosine deaminase gene family, ADAR3, contains both single- and double-stranded RNA binding domains. RNA 6:755–67
     [Google Scholar]
  60. 60. 
    Mladenova D, Barry G, Konen LM, Pineda SS, Guennewig B et al. 2018. Adar3 is involved in learning and memory in mice. Front. Neurosci. 12:243
     [Google Scholar]
  61. 61. 
    Wang Y, Chung DH, Monteleone LR, Li J, Chiang Y et al. 2019. RNA binding candidates for human ADAR3 from substrates of a gain of function mutant expressed in neuronal cells. Nucleic Acids Res 47:10801–14
     [Google Scholar]
  62. 62. 
    Oakes E, Anderson A, Cohen-Gadol A, Hundley HA. 2017. Adenosine deaminase that acts on RNA 3 (ADAR3) binding to glutamate receptor subunit B pre-mRNA inhibits RNA editing in glioblastoma. J. Biol. Chem. 292:4326–35
     [Google Scholar]
  63. 63. 
    Cattaneo R, Schmid A, Eschle D, Baczko K, ter Meulen V, Billeter MA. 1988. Biased hypermutation and other genetic changes in defective measles viruses in human brain infections. Cell 55:255–65
     [Google Scholar]
  64. 64. 
    Toth AM, Li Z, Cattaneo R, Samuel CE. 2009. RNA-specific adenosine deaminase ADAR1 suppresses measles virus-induced apoptosis and activation of protein kinase PKR. J. Biol. Chem. 284:29350–56
     [Google Scholar]
  65. 65. 
    Okonski KM, Samuel CE. 2013. Stress granule formation induced by measles virus is protein kinase PKR dependent and impaired by RNA adenosine deaminase ADAR1. J. Virol. 87:756–66
     [Google Scholar]
  66. 66. 
    Li Z, Okonski KM, Samuel CE. 2012. Adenosine deaminase acting on RNA 1 (ADAR1) suppresses the induction of interferon by measles virus. J. Virol. 86:3787–94
     [Google Scholar]
  67. 67. 
    Pfaller CK, Radeke MJ, Cattaneo R, Samuel CE. 2014. Measles virus C protein impairs production of defective copyback double-stranded viral RNA and activation of protein kinase R. J. Virol. 88:456–68
     [Google Scholar]
  68. 68. 
    Pfaller CK, Mastorakos GM, Matchett WE, Ma X, Samuel CE, Cattaneo R. 2015. Measles virus defective interfering RNAs are generated frequently and early in the absence of C protein and can be destabilized by adenosine deaminase acting on RNA-1-like hypermutations. J. Virol. 89:7735–47
     [Google Scholar]
  69. 69. 
    Toth AM, Devaux P, Cattaneo R, Samuel CE. 2009. Protein kinase PKR mediates the apoptosis induction and growth restriction phenotypes of C protein-deficient measles virus. J. Virol. 83:961–68
     [Google Scholar]
  70. 70. 
    McAllister CS, Toth AM, Zhang P, Devaux P, Cattaneo R, Samuel CE. 2010. Mechanisms of protein kinase PKR-mediated amplification of beta interferon induction by C protein-deficient measles virus. J. Virol. 84:380–86
     [Google Scholar]
  71. 71. 
    Chung H, Calis JJA, Wu X, Sun T, Yu Y et al. 2018. Human ADAR1 prevents endogenous RNA from triggering translational shutdown. Cell 172:811–24.e14
     [Google Scholar]
  72. 72. 
    Ahmad S, Mu X, Yang F, Greenwald E, Park JW et al. 2018. Breaching self-tolerance to Alu duplex RNA underlies MDA5-mediated inflammation. Cell 172:797–810.e13
     [Google Scholar]
  73. 73. 
    Nie Y, Hammond GL, Yang JH. 2007. Double-stranded RNA deaminase ADAR1 increases host susceptibility to virus infection. J. Virol. 81:917–23
     [Google Scholar]
  74. 74. 
    Li Z, Wolff KC, Samuel CE. 2010. RNA adenosine deaminase ADAR1 deficiency leads to increased activation of protein kinase PKR and reduced vesicular stomatitis virus growth following interferon treatment. Virology 396:316–22
     [Google Scholar]
  75. 75. 
    Yang S, Deng P, Zhu Z, Zhu J, Wang G et al. 2014. Adenosine deaminase acting on RNA1 limits RIG-I RNA detection and suppresses IFN production responding to viral and endogenous RNAs. J. Immunol. 193:3436–45
     [Google Scholar]
  76. 76. 
    Li Y, Banerjee S, Goldstein SA, Dong B, Gaughan C et al. 2017. Ribonuclease L mediates the cell-lethal phenotype of double-stranded RNA editing enzyme ADAR1 deficiency in a human cell line. eLife 6:e25687
     [Google Scholar]
  77. 77. 
    Nakahama T, Kato Y, Kim JI, Vongpipatana T, Suzuki Y et al. 2018. ADAR1-mediated RNA editing is required for thymic self-tolerance and inhibition of autoimmunity. EMBO Rep 19:e46303
     [Google Scholar]
  78. 78. 
    George CX, Samuel CE. 2011. Host response to polyomavirus infection is modulated by RNA adenosine deaminase ADAR1 but not by ADAR2. J. Virol. 85:8338–47
     [Google Scholar]
  79. 79. 
    Wang Y, Samuel CE. 2009. Adenosine deaminase ADAR1 increases gene expression at the translational level by decreasing protein kinase PKR-dependent eIF-2α phosphorylation. J. Mol. Biol. 393:777–87
     [Google Scholar]
  80. 80. 
    Bou-Nader C, Gordon JM, Henderson FE, Zhang J. 2019. The search for a PKR code-differential regulation of protein kinase R activity by diverse RNA and protein regulators. RNA 25:539–56
     [Google Scholar]
  81. 81. 
    Whitfield ZJ, Prasad AN, Ronk AJ, Kuzmin IV, Ilinykh PA et al. 2020. Species-specific evolution of Ebola virus during replication in human and bat cells. Cell Rep 32:108028
     [Google Scholar]
  82. 82. 
    Zahn RC, Schelp I, Utermöhlen O, von Laer D 2007. A-to-G hypermutation in the genome of lymphocytic choriomeningitis virus. J. Virol. 81:457–64
     [Google Scholar]
  83. 83. 
    Yanai M, Kojima S, Sakai M, Komorizono R, Tomonaga K, Makino A. 2020. ADAR2 is involved in self and nonself recognition of Borna disease virus genomic RNA in the nucleus. J. Virol. 94:e01513-19
     [Google Scholar]
  84. 84. 
    Cao Y, Cao R, Huang Y, Zhou H, Liu Y et al. 2018. A comprehensive study on cellular RNA editing activity in response to infections with different subtypes of influenza A viruses. BMC Genom 19:925
     [Google Scholar]
  85. 85. 
    Sarvestani ST, Tate MD, Moffat JM, Jacobi AM, Behlke MA et al. 2014. Inosine-mediated modulation of RNA sensing by Toll-like receptor 7 (TLR7) and TLR8. J. Virol. 88:799–810
     [Google Scholar]
  86. 86. 
    Suspène R, Petit V, Puyraimond-Zemmour D, Aynaud MM, Henry M et al. 2011. Double-stranded RNA adenosine deaminase ADAR-1-induced hypermutated genomes among inactivated seasonal influenza and live attenuated measles virus vaccines. J. Virol. 85:2458–62
     [Google Scholar]
  87. 87. 
    Vogel OA, Han J, Liang CY, Manicassamy S, Perez JT, Manicassamy B. 2020. The p150 isoform of ADAR1 blocks sustained RLR signaling and apoptosis during influenza virus infection. PLOS Pathog 16:e1008842
     [Google Scholar]
  88. 88. 
    Zhang T, Yin C, Boyd DF, Quarato G, Ingram JP et al. 2020. Influenza virus Z-RNAs induce ZBP1-mediated necroptosis. Cell 180:1115–29.e13
     [Google Scholar]
  89. 89. 
    Fensterl V, Chattopadhyay S, Sen GC. 2015. No love lost between viruses and interferons. Annu. Rev. Virol. 2:549–72
     [Google Scholar]
  90. 90. 
    de Chassey B, Aublin-Gex A, Ruggieri A, Meyniel-Schicklin L, Pradezynski F et al. 2013. The interactomes of influenza virus NS1 and NS2 proteins identify new host factors and provide insights for ADAR1 playing a supportive role in virus replication. PLOS Pathog 9:e1003440
     [Google Scholar]
  91. 91. 
    Biron CA, Nguyen KB, Pien GC. 2002. Innate immune responses to LCMV infections: natural killer cells and cytokines. Curr. Top. Microbiol. Immunol. 263:7–27
     [Google Scholar]
  92. 92. 
    Suspène R, Renard M, Henry M, Guétard D, Puyraimond-Zemmour D et al. 2008. Inversing the natural hydrogen bonding rule to selectively amplify GC-rich ADAR-edited RNAs. Nucleic Acids Res 36:e72
     [Google Scholar]
  93. 93. 
    Schoggins JW, Wilson SJ, Panis M, Murphy MY, Jones CT et al. 2011. A diverse range of gene products are effectors of the type I interferon antiviral response. Nature 472:481–85
     [Google Scholar]
  94. 94. 
    Clavarino G, Cláudio N, Couderc T, Dalet A, Judith D et al. 2012. Induction of GADD34 is necessary for dsRNA-dependent interferon-β production and participates in the control of Chikungunya virus infection. PLOS Pathog 8:e1002708
     [Google Scholar]
  95. 95. 
    Khrustalev VV, Khrustaleva TA, Sharma N, Giri R. 2017. Mutational pressure in Zika virus: local ADAR-editing areas associated with pauses in translation and replication. Front. Cell. Infect. Microbiol. 7:44
     [Google Scholar]
  96. 96. 
    Piontkivska H, Frederick M, Miyamoto MM, Wayne ML. 2017. RNA editing by the host ADAR system affects the molecular evolution of the Zika virus. Ecol. Evol. 7:4475–85
     [Google Scholar]
  97. 97. 
    McGrath EL, Rossi SL, Gao J, Widen SG, Grant AC et al. 2017. Differential responses of human fetal brain neural stem cells to Zika virus infection. Stem Cell Rep 8:715–27
     [Google Scholar]
  98. 98. 
    Zhou S, Yang C, Zhao F, Huang Y, Lin Y et al. 2019. Double-stranded RNA deaminase ADAR1 promotes the Zika virus replication by inhibiting the activation of protein kinase PKR. J. Biol. Chem. 294:18168–80
     [Google Scholar]
  99. 99. 
    Piontkivska H, Plonski NM, Miyamoto MM, Wayne ML. 2019. Explaining pathogenicity of congenital Zika and Guillain-Barré syndromes: Does dysregulation of RNA editing play a role?. Bioessays 41:e1800239
     [Google Scholar]
  100. 100. 
    Diosa-Toro M, Echavarría-Consuegra L, Flipse J, Fernández GJ, Kluiver J et al. 2017. MicroRNA profiling of human primary macrophages exposed to dengue virus identifies miRNA-3614-5p as antiviral and regulator of ADAR1 expression. PLOS Negl. Trop. Dis. 11:e0005981
     [Google Scholar]
  101. 101. 
    Paul D, Madan V, Bartenschlager R. 2014. Hepatitis C virus RNA replication and assembly: living on the fat of the land. Cell Host Microbe 16:569–79
     [Google Scholar]
  102. 102. 
    Luo S, Cassidy W, Jeffers L, Reddy KR, Bruno C, Howell CD. 2005. Interferon-stimulated gene expression in black and white hepatitis C patients during peginterferon alfa-2a combination therapy. Clin. Gastroenterol. Hepatol. 3:499–506
     [Google Scholar]
  103. 103. 
    Salvetat N, Van der Laan S, Vire B, Chimienti F, Cleophax S et al. 2019. RNA editing blood biomarkers for predicting mood alterations in HCV patients. J. Neurovirol. 25:825–36
     [Google Scholar]
  104. 104. 
    Garaigorta U, Chisari FV. 2009. Hepatitis C virus blocks interferon effector function by inducing protein kinase R phosphorylation. Cell Host Microbe 6:513–22
     [Google Scholar]
  105. 105. 
    Pujantell M, Franco S, Galván-Femenía I, Badia R, Castellví M et al. 2018. ADAR1 affects HCV infection by modulating innate immune response. Antivir. Res. 156:116–27
     [Google Scholar]
  106. 106. 
    Taylor DR, Puig M, Darnell ME, Mihalik K, Feinstone SM. 2005. New antiviral pathway that mediates hepatitis C virus replicon interferon sensitivity through ADAR1. J. Virol. 79:6291–98
     [Google Scholar]
  107. 107. 
    Li Y, Masaki T, Shimakami T, Lemon SM. 2014. hnRNP L and NF90 interact with hepatitis C virus 5′-terminal untranslated RNA and promote efficient replication. J. Virol. 88:7199–209
     [Google Scholar]
  108. 108. 
    Liu CX, Li X, Nan F, Jiang S, Gao X et al. 2019. Structure and degradation of circular RNAs regulate PKR activation in innate immunity. Cell 177:865–80.e21
     [Google Scholar]
  109. 109. 
    Ivanov A, Memczak S, Wyler E, Torti F, Porath HT et al. 2015. Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals. Cell Rep 10:170–77
     [Google Scholar]
  110. 110. 
    Sa Ribero M, Jouvenet N, Dreux M, Nisole S. 2020. Interplay between SARS-CoV-2 and the type I interferon response. PLOS Pathog 16:e1008737
     [Google Scholar]
  111. 111. 
    Niemeyer D, Zillinger T, Muth D, Zielecki F, Horvath G et al. 2013. Middle East respiratory syndrome coronavirus accessory protein 4a is a type I interferon antagonist. J. Virol. 87:12489–95
     [Google Scholar]
  112. 112. 
    Thornbrough JM, Jha BK, Yount B, Goldstein SA, Li Y et al. 2016. Middle East respiratory syndrome coronavirus NS4b protein inhibits host RNase L activation. mBio 7:e00258
     [Google Scholar]
  113. 113. 
    Zhao L, Jha BK, Wu A, Elliott R, Ziebuhr J et al. 2012. Antagonism of the interferon-induced OAS-RNase L pathway by murine coronavirus ns2 protein is required for virus replication and liver pathology. Cell Host Microbe 11:607–16
     [Google Scholar]
  114. 114. 
    Deng X, Hackbart M, Mettelman RC, O'Brien A, Mielech AM et al. 2017. Coronavirus nonstructural protein 15 mediates evasion of dsRNA sensors and limits apoptosis in macrophages. PNAS 114:E4251–60
     [Google Scholar]
  115. 115. 
    Di Giorgio S, Martignano F, Torcia MG, Mattiuz G, Conticello SG. 2020. Evidence for host-dependent RNA editing in the transcriptome of SARS-CoV-2. Sci. Adv. 6:eabb5813
     [Google Scholar]
  116. 116. 
    Wang R, Hozumi Y, Zheng YH, Yin C, Wei GW. 2020. Host immune response driving SARS-CoV-2 evolution. Viruses 12:1095
     [Google Scholar]
  117. 117. 
    Tao Y, Farsetta DL, Nibert ML, Harrison SC. 2002. RNA synthesis in a cage—structural studies of reovirus polymerase λ3. Cell 111:733–45
     [Google Scholar]
  118. 118. 
    Liu Y, Wolff KC, Jacobs BL, Samuel CE. 2001. Vaccinia virus E3L interferon resistance protein inhibits the interferon-induced adenosine deaminase A-to-I editing activity. Virology 289:378–87
     [Google Scholar]
  119. 119. 
    Kumar M, Carmichael GG 1997. Nuclear antisense RNA induces extensive adenosine modifications and nuclear retention of target transcripts. PNAS 94:3542–47
     [Google Scholar]
  120. 120. 
    Gu R, Zhang Z, DeCerbo JN, Carmichael GG. 2009. Gene regulation by sense-antisense overlap of polyadenylation signals. RNA 15:1154–63
     [Google Scholar]
  121. 121. 
    Chiang C, Pauli EK, Biryukov J, Feister KF, Meng M et al. 2018. The human papillomavirus E6 oncoprotein targets USP15 and TRIM25 to suppress RIG-I-mediated innate immune signaling. J. Virol. 92:e01737-17
     [Google Scholar]
  122. 122. 
    Pujantell M, Badia R, Galván-Femenía I, Garcia-Vidal E, de Cid R et al. 2019. ADAR1 function affects HPV replication and is associated to recurrent human papillomavirus-induced dysplasia in HIV coinfected individuals. Sci. Rep 9:19848
     [Google Scholar]
  123. 123. 
    Diao MK, Liu CY, Liu HW, Li JT, Li F et al. 2015. Integrated HPV genomes tend to integrate in gene desert areas in the CaSki, HeLa, and SiHa cervical cancer cell lines. Life Sci 127:46–52
     [Google Scholar]
  124. 124. 
    Gandy SZ, Linnstaedt SD, Muralidhar S, Cashman KA, Rosenthal LJ, Casey JL. 2007. RNA editing of the human herpesvirus 8 kaposin transcript eliminates its transforming activity and is induced during lytic replication. J. Virol. 81:13544–51
     [Google Scholar]
  125. 125. 
    Iizasa H, Wulff BE, Alla NR, Maragkakis M, Megraw M et al. 2010. Editing of Epstein-Barr virus-encoded BART6 microRNAs controls their dicer targeting and consequently affects viral latency. J. Biol. Chem. 285:33358–70
     [Google Scholar]
  126. 126. 
    Cao S, Moss W, O'Grady T, Concha M, Strong MJ et al. 2015. New noncoding lytic transcripts derived from the Epstein-Barr virus latency origin of replication, oriP, are hyperedited, bind the paraspeckle protein, NONO/p54nrb, and support viral lytic transcription. J. Virol. 89:7120–32
     [Google Scholar]
  127. 127. 
    Rosani U, Bai CM, Maso L, Shapiro M, Abbadi M et al. 2019. A-to-I editing of Malacoherpesviridae RNAs supports the antiviral role of ADAR1 in mollusks. BMC Evol. Biol. 19:149
     [Google Scholar]
  128. 128. 
    Lei T, Yuen KS, Tsao SW, Chen H, Kok KH, Jin DY 2013. Perturbation of biogenesis and targeting of Epstein-Barr virus-encoded miR-BART3 microRNA by adenosine-to-inosine editing. J. Gen. Virol. 94:2739–44
     [Google Scholar]
  129. 129. 
    Ishiguro S, Galipon J, Ishii R, Suzuki Y, Kondo S et al. 2018. Base-pairing probability in the microRNA stem region affects the binding and editing specificity of human A-to-I editing enzymes ADAR1-p110 and ADAR2. RNA Biol 15:976–89
     [Google Scholar]
  130. 130. 
    Pinto Y, Buchumenski I, Levanon EY, Eisenberg E. 2018. Human cancer tissues exhibit reduced A-to-I editing of miRNAs coupled with elevated editing of their targets. Nucleic Acids Res 46:71–82
     [Google Scholar]
  131. 131. 
    Kawahara Y, Megraw M, Kreider E, Iizasa H, Valente L et al. 2008. Frequency and fate of microRNA editing in human brain. Nucleic Acids Res 36:5270–80
     [Google Scholar]
  132. 132. 
    Paul D, Sinha AN, Ray A, Lal M, Nayak S et al. 2017. A-to-I editing in human miRNAs is enriched in seed sequence, influenced by sequence contexts and significantly hypoedited in glioblastoma multiforme. Sci. Rep. 7:2466
     [Google Scholar]
  133. 133. 
    Damania B. 2004. Oncogenic γ-herpesviruses: comparison of viral proteins involved in tumorigenesis. Nat. Rev. Microbiol. 2:656–68
     [Google Scholar]
  134. 134. 
    Pfeffer S, Zavolan M, Grässer FA, Chien M, Russo JJ et al. 2004. Identification of virus-encoded microRNAs. Science 304:734–36
     [Google Scholar]
  135. 135. 
    Arias C, Weisburd B, Stern-Ginossar N, Mercier A, Madrid AS et al. 2014. KSHV 2.0: A comprehensive annotation of the Kaposi's sarcoma-associated herpesvirus genome using next-generation sequencing reveals novel genomic and functional features. PLOS Pathog 10:e1003847
     [Google Scholar]
  136. 136. 
    Sommer B, Köhler M, Sprengel R, Seeburg PH. 1991. RNA editing in brain controls a determinant of ion flow in glutamate-gated channels. Cell 67:11–19
     [Google Scholar]
  137. 137. 
    Burns CM, Chu H, Rueter SM, Hutchinson LK, Canton H et al. 1997. Regulation of serotonin-2C receptor G-protein coupling by RNA editing. Nature 387:303–8
     [Google Scholar]
  138. 138. 
    Liu Y, Samuel CE. 1999. Editing of glutamate receptor subunit B pre-mRNA by splice-site variants of interferon-inducible double-stranded RNA-specific adenosine deaminase ADAR1. J. Biol. Chem. 274:5070–77
     [Google Scholar]
  139. 139. 
    Liu Y, Emeson RB, Samuel CE. 1999. Serotonin-2C receptor pre-mRNA editing in rat brain and in vitro by splice site variants of the interferon-inducible double-stranded RNA-specific adenosine deaminase ADAR1. J. Biol. Chem. 274:18351–58
     [Google Scholar]
  140. 140. 
    Lei M, Liu Y, Samuel CE. 1998. Adenovirus VAI RNA antagonizes the RNA-editing activity of the ADAR adenosine deaminase. Virology 245:188–96
     [Google Scholar]
  141. 141. 
    Kitajewski J, Schneider RJ, Safer B, Munemitsu SM, Samuel CE et al. 1986. Adenovirus VAI RNA antagonizes the antiviral action of interferon by preventing activation of the interferon-induced eIF-2α kinase. Cell 45:195–200
     [Google Scholar]
  142. 142. 
    Langland JO, Jacobs BL. 2004. Inhibition of PKR by vaccinia virus: role of the N- and C-terminal domains of E3L. Virology 324:419–29
     [Google Scholar]
  143. 143. 
    Zhang P, Jacobs BL, Samuel CE. 2008. Loss of protein kinase PKR expression in human HeLa cells complements the vaccinia virus E3L deletion mutant phenotype by restoration of viral protein synthesis. J. Virol. 82:840–48
     [Google Scholar]
  144. 144. 
    Kim YG, Muralinath M, Brandt T, Pearcy M, Hauns K et al. 2003. A role for Z-DNA binding in vaccinia virus pathogenesis. PNAS 100:6974–79
     [Google Scholar]
  145. 145. 
    Liao GR, Tseng YY, Tseng CY, Lin FY, Yamada Y et al. 2019. Adenosine deaminase acting on RNA 1 associates with Orf virus OV20.0 and enhances viral replication. J. Virol. 93:e01912-18
     [Google Scholar]
  146. 146. 
    Bockmann JH, Stadler D, Xia Y, Ko C, Wettengel JM et al. 2019. Comparative analysis of the antiviral effects mediated by type I and III interferons in hepatitis B virus-infected hepatocytes. J. Infect. Dis. 220:567–77
     [Google Scholar]
  147. 147. 
    Liu G, Ma X, Wang Z, Wakae K, Yuan Y et al. 2019. Adenosine deaminase acting on RNA-1 (ADAR1) inhibits hepatitis B virus (HBV) replication by enhancing microRNA-122 processing. J. Biol. Chem. 294:14043–54
     [Google Scholar]
  148. 148. 
    Yuan L, Jia Q, Yang S, Idris NFB, Li Y et al. 2020. ADAR1 promotes HBV replication through its deaminase domain. Front. Biosci. (Landmark Ed.) 25:710–21
     [Google Scholar]
  149. 149. 
    Wu X, Xin Z, Zhu X, Pan L, Li Z et al. 2012. Polymorphisms in ADAR1 gene affect response to interferon alpha based therapy for chronic hepatitis B in Han Chinese. Antivir. Res. 94:272–75
     [Google Scholar]
  150. 150. 
    Wu X, Shi W, Wu J, Zhu X, Chen K et al. 2014. A functional polymorphism in ADAR1 gene affects HBsAg seroclearance both spontaneously and interferon induced. Liver Int 34:1560–65
     [Google Scholar]
  151. 151. 
    Jung S, Altstetter SM, Protzer U. 2020. Innate immune recognition and modulation in hepatitis D virus infection. World J. Gastroenterol. 26:2781–91
     [Google Scholar]
  152. 152. 
    Jayan GC, Casey JL. 2002. Inhibition of hepatitis delta virus RNA editing by short inhibitory RNA-mediated knockdown of ADAR1 but not ADAR2 expression. J. Virol. 76:12399–404
     [Google Scholar]
  153. 153. 
    Wong SK, Lazinski DW. 2002. Replicating hepatitis delta virus RNA is edited in the nucleus by the small form of ADAR1. PNAS 99:15118–23
     [Google Scholar]
  154. 154. 
    Casey JL. 2006. RNA editing in hepatitis delta virus. Curr. Top. Microbiol. Immunol. 307:67–89
     [Google Scholar]
  155. 155. 
    Jayan GC, Casey JL. 2002. Increased RNA editing and inhibition of hepatitis delta virus replication by high-level expression of ADAR1 and ADAR2. J. Virol. 76:3819–27
     [Google Scholar]
  156. 156. 
    Radetskyy R, Daher A, Gatignol A. 2018. ADAR1 and PKR, interferon stimulated genes with clashing effects on HIV-1 replication. Cytokine Growth Factor Rev 40:48–58
     [Google Scholar]
  157. 157. 
    Phuphuakrat A, Kraiwong R, Boonarkart C, Lauhakirti D, Lee TH, Auewarakul P. 2008. Double-stranded RNA adenosine deaminases enhance expression of human immunodeficiency virus type 1 proteins. J. Virol. 82:10864–72
     [Google Scholar]
  158. 158. 
    Clerzius G, Gélinas JF, Daher A, Bonnet M, Meurs EF, Gatignol A. 2009. ADAR1 interacts with PKR during human immunodeficiency virus infection of lymphocytes and contributes to viral replication. J. Virol. 83:10119–28
     [Google Scholar]
  159. 159. 
    Doria M, Neri F, Gallo A, Farace MG, Michienzi A. 2009. Editing of HIV-1 RNA by the double-stranded RNA deaminase ADAR1 stimulates viral infection. Nucleic Acids Res 37:5848–58
     [Google Scholar]
  160. 160. 
    Pujantell M, Riveira-Muñoz E, Badia R, Castellví M, Garcia-Vidal E et al. 2017. RNA editing by ADAR1 regulates innate and antiviral immune functions in primary macrophages. Sci. Rep. 7:13339
     [Google Scholar]
  161. 161. 
    Doria M, Tomaselli S, Neri F, Ciafrè SA, Farace MG et al. 2011. ADAR2 editing enzyme is a novel human immunodeficiency virus-1 proviral factor. J. Gen. Virol. 92:1228–32
     [Google Scholar]
  162. 162. 
    Gélinas JF, Clerzius G, Shaw E, Gatignol A 2011. Enhancement of replication of RNA viruses by ADAR1 via RNA editing and inhibition of RNA-activated protein kinase. J. Virol. 85:8460–66
     [Google Scholar]
  163. 163. 
    Chukwurah E, Handy I, Patel RC. 2017. ADAR1 and PACT contribute to efficient translation of transcripts containing HIV-1 trans-activating response (TAR) element. Biochem. J. 474:1241–57
     [Google Scholar]
  164. 164. 
    Orecchini E, Federico M, Doria M, Arenaccio C, Giuliani E et al. 2015. The ADAR1 editing enzyme is encapsidated into HIV-1 virions. Virology 485:475–80
     [Google Scholar]
  165. 165. 
    Harris RS, Hultquist JF, Evans DT. 2012. The restriction factors of human immunodeficiency virus. J. Biol. Chem. 287:40875–83
     [Google Scholar]
  166. 166. 
    Zheng Y, Lorenzo C, Beal PA. 2017. DNA editing in DNA/RNA hybrids by adenosine deaminases that act on RNA. Nucleic Acids Res 45:3369–77
     [Google Scholar]
  167. 167. 
    Orecchini E, Frassinelli L, Galardi S, Ciafrè SA, Michienzi A. 2018. Post-transcriptional regulation of LINE-1 retrotransposition by AID/APOBEC and ADAR deaminases. Chromosome Res 26:45–59
     [Google Scholar]
  168. 168. 
    Orecchini E, Doria M, Antonioni A, Galardi S, Ciafrè SA et al. 2017. ADAR1 restricts LINE-1 retrotransposition. Nucleic Acids Res 45:155–68
     [Google Scholar]
  169. 169. 
    Hajjar AM, Linial ML. 1995. Modification of retroviral RNA by double-stranded RNA adenosine deaminase. J. Virol. 69:5878–82
     [Google Scholar]
  170. 170. 
    Felder MP, Laugier D, Yatsula B, Dezélée P, Calothy G, Marx M. 1994. Functional and biological properties of an avian variant long terminal repeat containing multiple A to G conversions in the U3 sequence. J. Virol. 68:4759–67
     [Google Scholar]
  171. 171. 
    Ko NL, Birlouez E, Wain-Hobson S, Mahieux R, Vartanian JP. 2012. Hyperediting of human T-cell leukemia virus type 2 and simian T-cell leukemia virus type 3 by the dsRNA adenosine deaminase ADAR-1. J. Gen. Virol. 93:2646–51
     [Google Scholar]
  172. 172. 
    Cachat A, Alais S, Chevalier SA, Journo C, Fusil F et al. 2014. ADAR1 enhances HTLV-1 and HTLV-2 replication through inhibition of PKR activity. Retrovirology 11:93
     [Google Scholar]
  173. 173. 
    Li S, Min JY, Krug RM, Sen GC. 2006. Binding of the influenza A virus NS1 protein to PKR mediates the inhibition of its activation by either PACT or double-stranded RNA. Virology 349:13–21
     [Google Scholar]
  174. 174. 
    Chilibeck KA, Wu T, Liang C, Schellenberg MJ, Gesner EM et al. 2006. FRET analysis of in vivo dimerization by RNA-editing enzymes. J. Biol. Chem. 281:16530–35
     [Google Scholar]
  175. 175. 
    Thuy-Boun AS, Thomas JM, Grajo HL, Palumbo CM, Park S et al. 2020. Asymmetric dimerization of adenosine deaminase acting on RNA facilitates substrate recognition. Nucleic Acids Res 48:7958–72
     [Google Scholar]
  176. 176. 
    Tariq A, Garncarz W, Handl C, Balik A, Pusch O, Jantsch MF. 2013. RNA-interacting proteins act as site-specific repressors of ADAR2-mediated RNA editing and fluctuate upon neuronal stimulation. Nucleic Acids Res 41:2581–93
     [Google Scholar]
  177. 177. 
    Shanmugam R, Zhang F, Srinivasan H, Richard JLC, Liu KI et al. 2018. SRSF9 selectively represses ADAR2-mediated editing of brain-specific sites in primates. Nucleic Acids Res 46:7379–95
     [Google Scholar]
  178. 178. 
    Quinones-Valdez G, Tran SS, Jun HI, Bahn JH, Yang EW et al. 2019. Regulation of RNA editing by RNA-binding proteins in human cells. Commun. Biol. 2:19
     [Google Scholar]
  179. 179. 
    Aktaş T, Avşar Ilık İ, Maticzka D, Bhardwaj V, Pessoa Rodrigues C et al. 2017. DHX9 suppresses RNA processing defects originating from the Alu invasion of the human genome. Nature 544:115–19
     [Google Scholar]
  180. 180. 
    Freund EC, Sapiro AL, Li Q, Linder S, Moresco JJ et al. 2020. Unbiased identification of trans regulators of ADAR and A-to-I RNA editing. Cell Rep 31:107656
     [Google Scholar]
  181. 181. 
    Sapiro AL, Freund EC, Restrepo L, Qiao HH, Bhate A et al. 2020. Zinc finger RNA-binding protein Zn72D regulates ADAR-mediated RNA editing in neurons. Cell Rep 31:107654
     [Google Scholar]
  182. 182. 
    van den Hoogen BG, van Boheemen S, de Rijck J, van Nieuwkoop S, Smith DJ et al. 2014. Excessive production and extreme editing of human metapneumovirus defective interfering RNA is associated with type I IFN induction. J. Gen. Virol. 95:1625–33
     [Google Scholar]
  183. 183. 
    Nguyen TA, Smith BRC, Tate MD, Belz GT, Barrios MH et al. 2017. SIDT2 transports extracellular dsRNA into the cytoplasm for innate immune recognition. Immunity 47:498–509.e6
     [Google Scholar]
  184. 184. 
    Nguyen TA, Smith BRC, Elgass KD, Creed SJ, Cheung S et al. 2019. SIDT1 localizes to endolysosomes and mediates double-stranded RNA transport into the cytoplasm. J. Immunol. 202:3483–92
     [Google Scholar]
/content/journals/10.1146/annurev-virology-091919-065320
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Adenosine Deaminases Acting on RNA (ADARs) and Viral Infections
Annual Review of Virology 8, 239 (2021); https://doi.org/10.1146/annurev-virology-091919-065320
/content/journals/10.1146/annurev-virology-091919-065320
/content/journals/10.1146/annurev-virology-091919-065320
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