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Abstract

Replication of the coronavirus genome requires continuous RNA synthesis, whereas transcription is a discontinuous process unique among RNA viruses. Transcription includes a template switch during the synthesis of subgenomic negative-strand RNAs to add a copy of the leader sequence. Coronavirus transcription is regulated by multiple factors, including the extent of base-pairing between transcription-regulating sequences of positive and negative polarity, viral and cell protein–RNA binding, and high-order RNA-RNA interactions. Coronavirus RNA synthesis is performed by a replication-transcription complex that includes viral and cell proteins that recognize -acting RNA elements mainly located in the highly structured 5′ and 3′ untranslated regions. In addition to many viral nonstructural proteins, the presence of cell nuclear proteins and the viral nucleocapsid protein increases virus amplification efficacy. Coronavirus RNA synthesis is connected with the formation of double-membrane vesicles and convoluted membranes. Coronaviruses encode proofreading machinery, unique in the RNA virus world, to ensure the maintenance of their large genome size.

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2015-11-09
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Literature Cited

  1. de Groot RJ, Baker SC, Baric R, Enjuanes L, Gorbalenya AE. 1.  et al. 2012. Coronaviridae. Virus Taxonomy: Ninth Report of the International Committee on Taxonomy of Viruses AMQ King, MJ Adams, EB Carstens, EJ Lefkowitz 774–96 San Diego, CA: Elsevier Academic [Google Scholar]
  2. Coleman CM, Frieman MB. 2.  2014. Coronaviruses: important emerging human pathogens. J. Virol. 88:5209–12 [Google Scholar]
  3. Marthaler D, Raymond L, Jiang Y, Collins J, Rossow K, Rovira A. 3.  2014. Rapid detection, complete genome sequencing, and phylogenetic analysis of porcine deltacoronavirus. Emerg. Infect. Dis. 20:1347–50 [Google Scholar]
  4. Huang YW, Dickerman AW, Pineyro P, Li L, Fang L. 4.  et al. 2013. Origin, evolution, and genotyping of emergent porcine epidemic diarrhea virus strains in the United States. mBio 4:e00737–13 [Google Scholar]
  5. Masters PS. 5.  2006. The molecular biology of coronaviruses. Adv. Virus Res. 66:193–292 [Google Scholar]
  6. Firth AE, Brierley I. 6.  2012. Non-canonical translation in RNA viruses. J. Gen. Virol. 93:1385–409 [Google Scholar]
  7. Enjuanes L, Almazan F, Sola I, Zuñiga S. 7.  2006. Biochemical aspects of coronavirus replication and virus-host interaction. Annu. Rev. Microbiol. 60:211–30 [Google Scholar]
  8. Lai MMC, Cavanagh D. 8.  1997. The molecular biology of coronaviruses. Adv. Virus Res. 48:1–100 [Google Scholar]
  9. Sola I, Mateos-Gomez PA, Almazan F, Zuñiga S, Enjuanes L. 9.  2011. RNA-RNA and RNA-protein interactions in coronavirus replication and transcription. RNA Biol. 8:237–48 [Google Scholar]
  10. Enjuanes L, Gorbalenya AE, de Groot RJ, Cowley JA, Ziebuhr J, Snijder EJ. 10.  2008. The Nidovirales. Encyclopedia of Virology BWJ Mahy, M Van Regenmortel, P Walker, D Majumder-Russell 419–30 Oxford, UK: Elsevier, 3rd ed.. [Google Scholar]
  11. Sawicki SG, Sawicki DL. 11.  1998. A new model for coronavirus transcription. Adv. Exp. Med. Biol. 440:215–19 [Google Scholar]
  12. van der Most RG, Spaan WJM. 12.  1995. Coronavirus replication, transcription, and RNA recombination. The Coronaviridae SG Siddell 11–31 New York: Plenum [Google Scholar]
  13. Miller WA, Koev G. 13.  2000. Synthesis of subgenomic RNAs by positive-strand RNA virus. Virology 273:1–8 [Google Scholar]
  14. Pasternak AO, Spaan WJ, Snijder EJ. 14.  2006. Nidovirus transcription: how to make sense?. J. Gen. Virol. 87:1403–21 [Google Scholar]
  15. Huang C, Lokugamage KG, Rozovics JM, Narayanan K, Semler BL, Makino S. 15.  2011. SARS coronavirus nsp1 protein induces template-dependent endonucleolytic cleavage of mRNAs: viral mRNAs are resistant to nsp1-induced RNA cleavage. PLOS Pathog. 7:e1002433 [Google Scholar]
  16. Alonso S, Izeta A, Sola I, Enjuanes L. 16.  2002. Transcription regulatory sequences and mRNA expression levels in the coronavirus transmissible gastroenteritis virus. J. Virol. 76:1293–308 [Google Scholar]
  17. Zuñiga S, Sola I, Alonso S, Enjuanes L. 17.  2004. Sequence motifs involved in the regulation of discontinuous coronavirus subgenomic RNA synthesis. J. Virol. 78:980–94Proposes a working model of coronavirus transcription based on the role of transcription-regulating sequence complementarity. [Google Scholar]
  18. Pasternak AO, van den Born E, Spaan WJ, Snijder EJ. 18.  2001. Sequence requirements for RNA strand transfer during nidovirus discontinuous subgenomic RNA synthesis. EMBO J. 20:7220–28Describes the role of transcription-regulating sequence complementarity in arterivirus transcription. [Google Scholar]
  19. van Marle G, Dobbe JC, Gultyaev AP, Luytjes W, Spaan WJM, Snijder EJ. 19.  1999. Arterivirus discontinuous mRNA transcription is guided by base pairing between sense and antisense transcription-regulating sequences. PNAS 96:12056–61 [Google Scholar]
  20. Pasternak AO, van den Born E, Spaan WJM, Snijder EJ. 20.  2003. The stability of the duplex between sense and antisense transcription-regulating sequences is a crucial factor in arterivirus subgenomic mRNA synthesis. J. Virol. 77:1175–83 [Google Scholar]
  21. Sola I, Moreno JL, Zuñiga S, Alonso S, Enjuanes L. 21.  2005. Role of nucleotides immediately flanking the transcription-regulating sequence core in coronavirus subgenomic mRNA synthesis. J. Virol. 79:2506–16Reports the relevance of sequence complementarity and transcription-regulating sequence composition in coronavirus transcription. [Google Scholar]
  22. Nagy PD, Simon AE. 22.  1997. New insights into the mechanisms of RNA recombination. Virology 235:1–9 [Google Scholar]
  23. Dufour D, Mateos-Gomez PA, Enjuanes L, Gallego J, Sola I. 23.  2011. Structure and functional relevance of a transcription-regulating sequence involved in coronavirus discontinuous RNA synthesis. J. Virol. 85:4963–73 [Google Scholar]
  24. Chang RY, Krishnan R, Brian DA. 24.  1996. The UCUAAAC promoter motif is not required for high-frequency leader recombination in bovine coronavirus defective interfering RNA. J. Virol. 70:2720–29 [Google Scholar]
  25. Moreno JL, Zuñiga S, Enjuanes L, Sola I. 25.  2008. Identification of a coronavirus transcription enhancer. J. Virol. 82:3882–93 [Google Scholar]
  26. Mateos-Gomez PA, Zuñiga S, Palacio L, Enjuanes L, Sola I. 26.  2011. Gene N proximal and distal RNA motifs regulate coronavirus nucleocapsid mRNA transcription. J. Virol. 85:8968–80 [Google Scholar]
  27. Mateos-Gomez PA, Morales L, Zuñiga S, Enjuanes L, Sola I. 27.  2013. Long-distance RNA-RNA interactions in the coronavirus genome form high-order structures promoting discontinuous RNA synthesis during transcription. J. Virol. 87:177–86Describes the longest RNA-RNA interaction known so far, leading to a high-order structure controlling coronavirus transcription. [Google Scholar]
  28. Nicholson BL, White KA. 28.  2014. Functional long-range RNA-RNA interactions in positive-strand RNA viruses. Nat. Rev. Microbiol. 12:493–504 [Google Scholar]
  29. Sawicki SG, Sawicki DL, Siddell SG. 29.  2007. A contemporary view of coronavirus transcription. J. Virol. 81:20–29 [Google Scholar]
  30. Almazan F, Galán C, Enjuanes L. 30.  2004. The nucleoprotein is required for efficient coronavirus genome replication. J. Virol. 78:12683–88 [Google Scholar]
  31. Zuñiga S, Cruz JL, Sola I, Mateos-Gomez PA, Palacio L, Enjuanes L. 31.  2010. Coronavirus nucleocapsid protein facilitates template switching and is required for efficient transcription. J. Virol. 84:2169–75Reports the relevance of the N protein in coronavirus transcription and template switching. [Google Scholar]
  32. Brockway SM, Lu XT, Peters TR, Dermody TS, Denison MR. 32.  2004. Intracellular localization and protein interactions of the gene 1 protein p28 during mouse hepatitis virus replication. J. Virol. 78:11551–62 [Google Scholar]
  33. Nedialkova DD, Gorbalenya AE, Snijder EJ. 33.  2010. Arterivirus nsp1 modulates the accumulation of minus-strand templates to control the relative abundance of viral mRNAs. PLOS Pathog. 6:e1000772 [Google Scholar]
  34. Wu CH, Chen PJ, Yeh SH. 34.  2014. Nucleocapsid phosphorylation and RNA helicase DDX1 recruitment enables coronavirus transition from discontinuous to continuous transcription. Cell Host Microbe 16:462–72 [Google Scholar]
  35. Plant EP, Dinman JD. 35.  2008. The role of programmed −1 ribosomal frameshifting in coronavirus propagation. Front. Biosci. 13:4873–81 [Google Scholar]
  36. Plant EP, Sims AC, Baric RS, Dinman JD, Taylor DR. 36.  2013. Altering SARS coronavirus frameshift efficiency affects genomic and subgenomic RNA production. Viruses 5:279–94 [Google Scholar]
  37. Imbert I, Guillemot JC, Bourhis JM, Bussetta C, Coutard B. 37.  et al. 2006. A second, non-canonical RNA-dependent RNA polymerase in SARS coronavirus. EMBO J. 25:4933–42 [Google Scholar]
  38. Knoops K, Kikkert M, Worm SH, Zevenhoven-Dobbe JC, van der Meer Y. 38.  et al. 2008. SARS-coronavirus replication is supported by a reticulovesicular network of modified endoplasmic reticulum. PLOS Biol. 6:e226 [Google Scholar]
  39. Gosert R, Kanjanahaluethai A, Egger D, Bienz K, Baker SC. 39.  2002. RNA replication of mouse hepatitis virus takes place at double-membrane vesicles. J. Virol. 76:3697–708 [Google Scholar]
  40. Ulasli M, Verheije MH, de Haan CA, Reggiori F. 40.  2010. Qualitative and quantitative ultrastructural analysis of the membrane rearrangements induced by coronavirus. Cell Microbiol. 12:844–61 [Google Scholar]
  41. Verheije MH, Raaben M, Mari M, te Lintelo EG, Reggiori F. 41.  et al. 2008. Mouse hepatitis coronavirus RNA replication depends on GBF1-mediated ARF1 activation. PLOS Pathog. 4:e1000088 [Google Scholar]
  42. Stokes HL, Baliji S, Hui CG, Sawicki SG, Baker SC, Siddell SG. 42.  2010. A new cistron in the murine hepatitis virus replicase gene. J. Virol. 84:10148–58 [Google Scholar]
  43. Hagemeijer MC, Vonk AM, Monastyrska I, Rottier PJ, de Haan CA. 43.  2012. Visualizing coronavirus RNA synthesis in time by using click chemistry. J. Virol. 86:5808–16 [Google Scholar]
  44. den Boon JA, Ahlquist P. 44.  2010. Organelle-like membrane compartmentalization of positive-strand RNA virus replication factories. Annu. Rev. Microbiol. 64:241–56 [Google Scholar]
  45. Angelini MM, Akhlaghpour M, Neuman BW, Buchmeier MJ. 45.  2013. Severe acute respiratory syndrome coronavirus nonstructural proteins 3, 4, and 6 induce double-membrane vesicles. mBio 4:e00524–13 [Google Scholar]
  46. Oostra M, Hagemeijer MC, van Gent M, Bekker CP, te Lintelo EG. 46.  et al. 2008. Topology and membrane anchoring of the coronavirus replication complex: Not all hydrophobic domains of nsp3 and nsp6 are membrane spanning. J. Virol. 82:12392–405 [Google Scholar]
  47. Gadlage MJ, Sparks JS, Beachboard DC, Cox RG, Doyle JD. 47.  et al. 2010. Murine hepatitis virus nonstructural protein 4 regulates virus-induced membrane modifications and replication complex function. J. Virol. 84:280–90 [Google Scholar]
  48. Hagemeijer MC, Monastyrska I, Griffith J, van der Sluijs P, Voortman J. 48.  et al. 2014. Membrane rearrangements mediated by coronavirus nonstructural proteins 3 and 4. Virology 458–59:125–35 [Google Scholar]
  49. Maier HJ, Hawes PC, Cottam EM, Mantell J, Verkade P. 49.  et al. 2013. Infectious bronchitis virus generates spherules from zippered endoplasmic reticulum membranes. mBio 4:e00801–13 [Google Scholar]
  50. Maier HJ, Hawes PC, Keep SM, Britton P. 50.  2014. Spherules and IBV. Bioengineered 5:288–92 [Google Scholar]
  51. Hagemeijer MC, Rottier PJ, de Haan CA. 51.  2012. Biogenesis and dynamics of the coronavirus replicative structures. Viruses 4:3245–69 [Google Scholar]
  52. Neuman BW, Angelini MM, Buchmeier MJ. 52.  2014. Does form meet function in the coronavirus replicative organelle?. Trends Microbiol. 22:642–47 [Google Scholar]
  53. Anderson P, Kedersha N. 53.  2008. Stress granules: the Tao of RNA triage. Trends Biochem. Sci. 33:141–50 [Google Scholar]
  54. Kedersha N, Stoecklin G, Ayodele M, Yacono P, Lykke-Andersen J. 54.  et al. 2005. Stress granules and processing bodies are dynamically linked sites of mRNP remodeling. J. Cell Biol. 169:871–84 [Google Scholar]
  55. Ruggieri A, Dazert E, Metz P, Hofmann S, Bergeest JP. 55.  et al. 2012. Dynamic oscillation of translation and stress granule formation mark the cellular response to virus infection. Cell Host Microbe 12:71–85 [Google Scholar]
  56. White JP, Lloyd RE. 56.  2012. Regulation of stress granules in virus systems. Trends Microbiol. 20:175–83 [Google Scholar]
  57. Reineke LC, Lloyd RE. 57.  2013. Diversion of stress granules and P-bodies during viral infection. Virology 436:255–67 [Google Scholar]
  58. Lindquist ME, Lifland AW, Utley TJ, Santangelo PJ, Crowe JE Jr. 58.  2010. Respiratory syncytial virus induces host RNA stress granules to facilitate viral replication. J. Virol. 84:12274–84 [Google Scholar]
  59. Raaben M, Groot Koerkamp MJ, Rottier PJ, de Haan CA. 59.  2007. Mouse hepatitis coronavirus replication induces host translational shutoff and mRNA decay, with concomitant formation of stress granules and processing bodies. Cell Microbiol. 9:2218–29 [Google Scholar]
  60. Sola I, Galán C, Mateos-Gomez PA, Palacio L, Zuñiga S. 60.  et al. 2011. The polypyrimidine tract-binding protein affects coronavirus RNA accumulation levels and relocalizes viral RNAs to novel cytoplasmic domains different from replication-transcription sites. J. Virol. 85:5136–49 [Google Scholar]
  61. Emmott E, Munday D, Bickerton E, Britton P, Rodgers MA. 61.  et al. 2013. The cellular interactome of the coronavirus infectious bronchitis virus nucleocapsid protein and functional implications for virus biology. J. Virol. 87:9486–500 [Google Scholar]
  62. Courtney SC, Scherbik SV, Stockman BM, Brinton MA. 62.  2012. West Nile virus infections suppress early viral RNA synthesis and avoid inducing the cell stress granule response. J. Virol. 86:3647–57 [Google Scholar]
  63. Onomoto K, Yoneyama M, Fung G, Kato H, Fujita T. 63.  2014. Antiviral innate immunity and stress granule responses. Trends Immunol. 35:420–28 [Google Scholar]
  64. Emmott E, Rodgers MA, Macdonald A, McCrory S, Ajuh P, Hiscox JA. 64.  2010. Quantitative proteomics using stable isotope labeling with amino acids in cell culture reveals changes in the cytoplasmic, nuclear, and nucleolar proteomes in Vero cells infected with the coronavirus infectious bronchitis virus. Mol. Cell. Proteomics 9:1920–36 [Google Scholar]
  65. Gustin KE, Sarnow P. 65.  2006. Positive-strand RNA viruses and the nucleus. Viruses and the Nucleus JA Hiscox 161–84 Chichester, UK: Wiley [Google Scholar]
  66. Wilhelmsen KC, Leibowitz JL, Bond CW, Robb JC. 66.  1981. The replication of murine coronaviruses in enucleated cells. Virology 110:225–30 [Google Scholar]
  67. Emmett SR, Dove B, Mahoney L, Wurm T, Hiscox JA. 67.  2005. The cell cycle and virus infection. Methods Mol. Biol. 296:197–218 [Google Scholar]
  68. Surjit M, Liu B, Chow VT, Lal SK. 68.  2006. The nucleocapsid protein of severe acute respiratory syndrome-coronavirus inhibits the activity of cyclin-cyclin-dependent kinase complex and blocks S phase progression in mammalian cells. J. Biol. Chem. 281:10669–81 [Google Scholar]
  69. Wurm T, Chen H, Hodgson T, Britton P, Brooks G, Hiscox JA. 69.  2001. Localization to the nucleolus is a common feature of coronavirus nucleoproteins, and the protein may disrupt host cell division. J. Virol. 75:9345–56 [Google Scholar]
  70. Cawood R, Harrison SM, Dove BK, Reed ML, Hiscox JA. 70.  2007. Cell cycle dependent nucleolar localization of the coronavirus nucleocapsid protein. Cell Cycle 6:863–67 [Google Scholar]
  71. Ding L, Huang Y, Du Q, Dong F, Zhao X. 71.  et al. 2014. TGEV nucleocapsid protein induces cell cycle arrest and apoptosis through activation of p53 signaling. Biochem. Biophys. Res. Commun. 445:497–503 [Google Scholar]
  72. Xu X, Zhang H, Zhang Q, Huang Y, Dong J. 72.  et al. 2013. Porcine epidemic diarrhea virus N protein prolongs S-phase cell cycle, induces endoplasmic reticulum stress, and up-regulates interleukin-8 expression. Vet. Microbiol. 164:212–21 [Google Scholar]
  73. Luo H, Chen Q, Chen J, Chen K, Shen X, Jiang H. 73.  2005. The nucleocapsid protein of SARS coronavirus has a high binding affinity to the human cellular heterogeneous nuclear ribonucleoprotein A1. FEBS Lett. 579:2623–28 [Google Scholar]
  74. Shen S, Wen ZL, Liu DX. 74.  2003. Emergence of a coronavirus infectious bronchitis virus mutant with a truncated 3b gene: functional characterization of the 3b protein in pathogenesis and replication. Virology 311:16–27 [Google Scholar]
  75. Khan S, Fielding BC, Tan TH, Chou CF, Shen S. 75.  et al. 2006. Over-expression of severe acute respiratory syndrome coronavirus 3b protein induces both apoptosis and necrosis in Vero E6 cells. Virus Res. 122:20–27 [Google Scholar]
  76. Yuan X, Yao Z, Shan Y, Chen B, Yang Z. 76.  et al. 2005. Nucleolar localization of non-structural protein 3b, a protein specifically encoded by the severe acute respiratory syndrome coronavirus. Virus Res. 114:70–79 [Google Scholar]
  77. Freundt EC, Yu L, Park E, Lenardo MJ, Xu XN. 77.  2009. Molecular determinants for subcellular localization of the severe acute respiratory syndrome coronavirus open reading frame 3b protein. J. Virol. 83:6631–40 [Google Scholar]
  78. Matthews KL, Coleman CM, van der Meer Y, Snijder EJ, Frieman MB. 78.  2014. The ORF4b-encoded accessory proteins of Middle East respiratory syndrome coronavirus and two related bat coronaviruses localize to the nucleus and inhibit innate immune signalling. J. Gen. Virol. 95:874–82 [Google Scholar]
  79. Hussain S, Gallagher T. 79.  2010. SARS-coronavirus protein 6 conformations required to impede protein import into the nucleus. Virus Res. 153:299–304 [Google Scholar]
  80. Frieman M, Yount B, Heise M, Kopecky-Bromberg SA, Palese P, Baric RS. 80.  2007. Severe acute respiratory syndrome coronavirus ORF6 antagonizes STAT1 function by sequestering nuclear import factors on the rough endoplasmic reticulum/Golgi membrane. J. Virol. 81:9812–24 [Google Scholar]
  81. Sharma K, Akerstrom S, Sharma AK, Chow VT, Teow S. 81.  et al. 2011. SARS-CoV 9b protein diffuses into nucleus, undergoes active Crm1 mediated nucleocytoplasmic export and triggers apoptosis when retained in the nucleus. PLOS ONE 6:e19436 [Google Scholar]
  82. Narayanan K, Ramirez SI, Lokugamage KG, Makino S. 82.  2015. Coronavirus nonstructural protein 1: common and distinct functions in the regulation of host and viral gene expression. Virus Res. 202:89–100 [Google Scholar]
  83. Huang C, Lokugamage KG, Rozovics JM, Narayanan K, Semler BL, Makino S. 83.  2011. Alphacoronavirus transmissible gastroenteritis virus nsp1 protein suppresses protein translation in mammalian cells and in cell-free HeLa cell extracts but not in rabbit reticulocyte lysate. J. Virol. 85:638–43 [Google Scholar]
  84. Li H, Zheng Z, Zhou P, Zhang B, Shi Z. 84.  et al. 2010. The cysteine protease domain of porcine reproductive and respiratory syndrome virus non-structural protein 2 antagonizes interferon regulatory factor 3 activation. J. Gen. Virol. 91:2947–58 [Google Scholar]
  85. Tijms MA, van der Meer Y, Snijder EJ. 85.  2002. Nuclear localization of non-structural protein 1 and nucleocapsid protein of equine arteritis virus. J. Gen. Virol. 83:795–800 [Google Scholar]
  86. Burgess HM, Gray NK. 86.  2012. An integrated model for the nucleo-cytoplasmic transport of cytoplasmic poly(A)-binding proteins. Commun. Integr. Biol. 5:243–47 [Google Scholar]
  87. Salaun C, MacDonald AI, Larralde O, Howard L, Lochtie K. 87.  et al. 2010. Poly(A)-binding protein 1 partially relocalizes to the nucleus during herpes simplex virus type 1 infection in an ICP27-independent manner and does not inhibit virus replication. J. Virol. 84:8539–48 [Google Scholar]
  88. Lee C, Hodgins D, Calvert JG, Welch SK, Jolie R, Yoo D. 88.  2006. Mutations within the nuclear localization signal of the porcine reproductive and respiratory syndrome virus nucleocapsid protein attenuate virus replication. Virology 346:238–50 [Google Scholar]
  89. Song C, Krell P, Yoo D. 89.  2010. Nonstructural protein 1α subunit-based inhibition of NF-κB activation and suppression of interferon-β production by porcine reproductive and respiratory syndrome virus. Virology 407:268–80 [Google Scholar]
  90. Han M, Du Y, Song C, Yoo D. 90.  2013. Degradation of CREB-binding protein and modulation of type I interferon induction by the zinc finger motif of the porcine reproductive and respiratory syndrome virus nsp1α subunit. Virus Res. 172:54–65 [Google Scholar]
  91. Kim O, Sun Y, Lai FW, Song C, Yoo D. 91.  2010. Modulation of type I interferon induction by porcine reproductive and respiratory syndrome virus and degradation of CREB-binding protein by non-structural protein 1 in MARC-145 and HeLa cells. Virology 402:315–26 [Google Scholar]
  92. Patel D, Nan Y, Shen M, Ritthipichai K, Zhu X, Zhang YJ. 92.  2010. Porcine reproductive and respiratory syndrome virus inhibits type I interferon signaling by blocking STAT1/STAT2 nuclear translocation. J. Virol. 84:11045–55 [Google Scholar]
  93. Chen Z, Lawson S, Sun Z, Zhou X, Guan X. 93.  et al. 2010. Identification of two auto-cleavage products of nonstructural protein 1 (nsp1) in porcine reproductive and respiratory syndrome virus infected cells: nsp1 function as interferon antagonist. Virology 398:87–97 [Google Scholar]
  94. Li HP, Huang P, Park S, Lai MMC. 94.  1999. Polypyrimidine tract-binding protein binds to the leader RNA of mouse hepatitis virus and serves as a regulator of viral transcription. J. Virol. 73:772–77 [Google Scholar]
  95. Galán C, Sola I, Nogales A, Thomas B, Akoulitchev A. 95.  et al. 2009. Host cell proteins interacting with the 3′ end of TGEV coronavirus genome influence virus replication. Virology 391:304–14 [Google Scholar]
  96. Choi KS, Huang P, Lai MM. 96.  2002. Polypyrimidine-tract-binding protein affects transcription but not translation of mouse hepatitis virus RNA. Virology 303:58–68 [Google Scholar]
  97. Choi KS, Mizutani A, Lai MM. 97.  2004. SYNCRIP, a member of the heterogeneous nuclear ribonucleoprotein family, is involved in mouse hepatitis virus RNA synthesis. J. Virol. 78:13153–62 [Google Scholar]
  98. Jia J, Arif A, Ray PS, Fox PL. 98.  2008. WHEP domains direct noncanonical function of glutamyl-prolyl tRNA synthetase in translational control of gene expression. Mol. Cell 29:679–90 [Google Scholar]
  99. Mukhopadhyay R, Jia J, Arif A, Ray PS, Fox PL. 99.  2009. The GAIT system: a gatekeeper of inflammatory gene expression. Trends Biochem. Sci. 34:324–31 [Google Scholar]
  100. Masters PS. 100.  2007. Genomic cis-acting elements in coronavirus RNA replication. Coronaviruses: Molecular and Cellular Biology V Thiel 65–80 Norfolk, UK: Caister Academic [Google Scholar]
  101. Madhugiri R, Fricke M, Marz M, Ziebuhr J. 101.  2014. RNA structure analysis of alphacoronavirus terminal genome regions. Virus Res. 194:76–89 [Google Scholar]
  102. Chen SC, Olsthoorn RC. 102.  2010. Group-specific structural features of the 5′-proximal sequences of coronavirus genomic RNAs. Virology 401:29–41 [Google Scholar]
  103. Kang H, Feng M, Schroeder ME, Giedroc DP, Leibowitz JL. 103.  2006. Putative cis-acting stem-loops in the 5′ untranslated region of the severe acute respiratory syndrome coronavirus can substitute for their mouse hepatitis virus counterparts. J. Virol. 80:10600–14 [Google Scholar]
  104. Li L, Kang H, Liu P, Makkinje N, Williamson ST. 104.  et al. 2008. Structural lability in stem-loop 1 drives a 5′ UTR–3′ UTR interaction in coronavirus replication. J. Mol. Biol. 377:790–803 [Google Scholar]
  105. Liu P, Li L, Keane SC, Yang D, Leibowitz JL, Giedroc DP. 105.  2009. Mouse hepatitis virus stem-loop 2 adopts a uYNMG(U)a-like tetraloop structure that is highly functionally tolerant of base substitutions. J. Virol. 83:12084–93 [Google Scholar]
  106. Lee CW, Li L, Giedroc DP. 106.  2011. The solution structure of coronaviral stem-loop 2 (SL2) reveals a canonical CUYG tetraloop fold. FEBS Lett. 585:1049–53 [Google Scholar]
  107. Raman S, Bouma P, Williams GD, Brian DA. 107.  2003. Stem-loop III in the 5′ untranslated region is a cis-acting element in bovine coronavirus defective interfering RNA replication. J. Virol. 77:6720–30 [Google Scholar]
  108. Yang D, Liu P, Giedroc DP, Leibowitz J. 108.  2011. Mouse hepatitis virus stem-loop 4 functions as a spacer element required to drive subgenomic RNA synthesis. J. Virol. 85:9199–209 [Google Scholar]
  109. Goebel SJ, Hsue B, Dombrowski TF, Masters PS. 109.  2004. Characterization of the RNA components of a putative molecular switch in the 3′ untranslated region of the murine coronavirus genome. J. Virol. 78:669–82 [Google Scholar]
  110. Zust R, Miller TB, Goebel SJ, Thiel V, Masters PS. 110.  2008. Genetic interactions between an essential 3′ cis-acting RNA pseudoknot, replicase gene products, and the extreme 3′ end of the mouse coronavirus genome. J. Virol. 82:1214–28Proposes a model for RNA synthesis initiation involving RNA structures and replicase components. [Google Scholar]
  111. Williams GD, Chang RY, Brian DA. 111.  1999. A phylogenetically conserved hairpin-type 3′ untranslated region pseudoknot functions in coronavirus RNA replication. J. Virol. 73:8349–55 [Google Scholar]
  112. Dalton K, Casais R, Shaw K, Stirrups K, Evans S. 112.  et al. 2001. cis-acting sequences required for coronavirus infectious bronchitis virus defective-RNA replication and packaging. J. Virol. 75:125–33 [Google Scholar]
  113. Liu Q, Johnson RF, Leibowitz JL. 113.  2001. Secondary structural elements within the 3′ untranslated region of mouse hepatitis virus strain JHM genomic RNA. J. Virol. 75:12105–13 [Google Scholar]
  114. Williams AK, Wang L, Sneed LW, Collisson EW. 114.  1993. Analysis of a hypervariable region in the 3′ non-coding end of the infectious bronchitis virus genome. Virus Res. 28:19–27 [Google Scholar]
  115. Goebel SJ, Miller TB, Bennett CJ, Bernard KA, Masters PS. 115.  2007. A hypervariable region within the 3′ cis-acting element of the murine coronavirus genome is nonessential for RNA synthesis but affects pathogenesis. J. Virol. 81:1274–87 [Google Scholar]
  116. Spagnolo JF, Hogue BG. 116.  2000. Host protein interactions with the 3′ end of bovine coronavirus RNA and the requirement of the poly(A) tail for coronavirus defective genome replication. J. Virol. 74:5053–65 [Google Scholar]
  117. Schelle B, Karl N, Ludewig B, Siddell SG, Thiel V. 117.  2005. Selective replication of coronavirus genomes that express nucleocapsid protein. J. Virol. 79:6620–30 [Google Scholar]
  118. Ziebuhr J. 118.  2005. The coronavirus replicase. Coronavirus Replication and Reverse Genetics L Enjuanes 57–94 Berlin: Springer-Verlag [Google Scholar]
  119. Ulferts R, Imbert I, Canard B, Ziebuhr J. 119.  2010. Expression and functions of SARS coronavirus replicative proteins. Molecular Biology of the SARS-Coronavirus SK Lal 75–98 Berlin: Springer-Verlag [Google Scholar]
  120. Gorbalenya AE, Enjuanes L, Ziebuhr J, Snijder EJ. 120.  2006. Nidovirales: evolving the largest RNA virus genome. Virus Res. 117:17–37 [Google Scholar]
  121. Xu X, Liu Y, Weiss S, Arnold E, Sarafianos SG, Ding J. 121.  2003. Molecular model of SARS coronavirus polymerase: implications for biochemical functions and drug design. Nucleic Acids Res. 31:7117–30 [Google Scholar]
  122. Cheng A, Zhang W, Xie Y, Jiang W, Arnold E. 122.  et al. 2005. Expression, purification, and characterization of SARS coronavirus RNA polymerase. Virology 335:165–76 [Google Scholar]
  123. Brockway SM, Clay CT, Lu XT, Denison MR. 123.  2003. Characterization of the expression, intracellular localization, and replication complex association of the putative mouse hepatitis virus RNA-dependent RNA polymerase. J. Virol. 77:10515–27 [Google Scholar]
  124. te Velthuis AJ, Arnold JJ, Cameron CE, van den Worm SH, Snijder EJ. 124.  2010. The RNA polymerase activity of SARS-coronavirus nsp12 is primer dependent. Nucleic Acids Res. 38:203–14 [Google Scholar]
  125. Ahn DG, Choi JK, Taylor DR, Oh JW. 125.  2012. Biochemical characterization of a recombinant SARS coronavirus nsp12 RNA-dependent RNA polymerase capable of copying viral RNA templates. Arch. Virol. 157:2095–104 [Google Scholar]
  126. te Velthuis AJ, van den Worm SH, Snijder EJ. 126.  2012. The SARS-coronavirus nsp7+nsp8 complex is a unique multimeric RNA polymerase capable of both de novo initiation and primer extension. Nucleic Acids Res. 40:1737–47 [Google Scholar]
  127. Zhai Y, Sun F, Li X, Pang H, Xu X. 127.  et al. 2005. Insights into SARS-CoV transcription and replication from the structure of the nsp7-nsp8 hexadecamer. Nat. Struct. Mol. Biol. 12:980–86 [Google Scholar]
  128. Imbert I, Snijder EJ, Dimitrova M, Guillemot JC, Lecine P, Canard B. 128.  2008. The SARS-coronavirus PLnc domain of nsp3 as a replication/transcription scaffolding protein. Virus Res. 133:136–48 [Google Scholar]
  129. Subissi L, Posthuma CC, Collet A, Zevenhoven-Dobbe JC, Gorbalenya AE. 129.  et al. 2014. One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities. PNAS 111:E3900–9Describes the coronavirus core RNA synthesis complex integrating polymerase, proofreading, and capping activities. [Google Scholar]
  130. Snijder EJ, Bredenbeek PJ, Dobbe JC, Thiel V, Ziebuhr J. 130.  et al. 2003. Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage. J. Mol. Biol. 331:991–1004Comprehensive bioinformatic predictions on the presence of unique enzymatic RNA-modifying activities in coronavirus genomes. [Google Scholar]
  131. Egloff MP, Ferron F, Campanacci V, Longhi S, Rancurel C. 131.  et al. 2004. The severe acute respiratory syndrome-coronavirus replicative protein nsp9 is a single-stranded RNA-binding subunit unique in the RNA virus world. PNAS 101:3792–96 [Google Scholar]
  132. Sutton G, Fry E, Carter L, Sainsbury S, Walter T. 132.  et al. 2004. The nsp9 replicase protein of SARS-coronavirus, structure and functional insights. Structure 12:341–53 [Google Scholar]
  133. Miknis ZJ, Donaldson EF, Umland TC, Rimmer RA, Baric RS, Schultz LW. 133.  2009. Severe acute respiratory syndrome coronavirus nsp9 dimerization is essential for efficient viral growth. J. Virol. 83:3007–18 [Google Scholar]
  134. Gorbalenya AE, Koonin EV, Donchenko AP, Blinov VM. 134.  1989. Coronavirus genome: prediction of putative functional domains in the non-structural polyprotein by comparative amino acid sequence analysis. Nucleic Acids Res. 17:4847–61 [Google Scholar]
  135. Seybert A, Posthuma CC, van Dinten LC, Snijder EJ, Gorbalenya AE, Ziebuhr J. 135.  2005. A complex zinc finger controls the enzymatic activities of nidovirus helicases. J. Virol. 79:696–704 [Google Scholar]
  136. Ivanov KA, Thiel V, Dobbe JC, van der Meer Y, Snijder EJ, Ziebuhr J. 136.  2004. Multiple enzymatic activities associated with severe acute respiratory syndrome coronavirus helicase. J. Virol. 78:5619–32 [Google Scholar]
  137. Seybert A, Hegyi A, Siddell SG, Ziebuhr J. 137.  2000. The human coronavirus 229E superfamily 1 helicase has RNA and DNA duplex-unwinding activities with 5′-to-3′ polarity. RNA 6:1056–68 [Google Scholar]
  138. Tanner JA, Watt RM, Chai YB, Lu LY, Lin MC. 138.  et al. 2003. The severe acute respiratory syndrome (SARS) coronavirus NTPase/helicase belongs to a distinct class of 5′ to 3′ viral helicases. J. Biol. Chem. 278:39578–82 [Google Scholar]
  139. Ivanov KA, Ziebuhr J. 139.  2004. Human coronavirus 229E nonstructural protein 13: characterization of duplex-unwinding, nucleoside triphosphatase, and RNA 5′-triphosphatase activities. J. Virol. 78:7833–38 [Google Scholar]
  140. Lee NR, Kwon HM, Park K, Oh S, Jeong YJ, Kim DE. 140.  2010. Cooperative translocation enhances the unwinding of duplex DNA by SARS coronavirus helicase nsp13. Nucleic Acids Res. 38:7626–36 [Google Scholar]
  141. Chen JY, Chen WN, Poon KM, Zheng BJ, Lin X. 141.  et al. 2009. Interaction between SARS-CoV helicase and a multifunctional cellular protein (Ddx5) revealed by yeast and mammalian cell two-hybrid systems. Arch. Virol. 154:507–12 [Google Scholar]
  142. Xu L, Khadijah S, Fang S, Wang L, Tay FP, Liu DX. 142.  2010. The cellular RNA helicase DDX1 interacts with coronavirus nonstructural protein 14 and enhances viral replication. J. Virol. 84:8571–83 [Google Scholar]
  143. Adedeji AO, Marchand B, te Velthuis AJ, Snijder EJ, Weiss S. 143.  et al. 2012. Mechanism of nucleic acid unwinding by SARS-CoV helicase. PLOS ONE 7:e36521 [Google Scholar]
  144. Minskaia E, Hertzig T, Gorbalenya AE, Campanacci V, Cambillau C. 144.  et al. 2006. Discovery of an RNA virus 3′→5′ exoribonuclease that is critically involved in coronavirus RNA synthesis. PNAS 103:5108–13 [Google Scholar]
  145. Chen Y, Cai H, Pan J, Xiang N, Tien P. 145.  et al. 2009. Functional screen reveals SARS coronavirus nonstructural protein nsp14 as a novel cap N7 methyltransferase. PNAS 106:3484–89 [Google Scholar]
  146. Denison MR, Graham RL, Donaldson EF, Eckerle LD, Baric RS. 146.  2011. Coronaviruses: An RNA proofreading machine regulates replication fidelity and diversity. RNA Biol. 8:270–79 [Google Scholar]
  147. Smith EC, Sexton NR, Denison MR. 147.  2014. Thinking outside the triangle: replication fidelity of the largest RNA viruses. Annu. Rev. Virol. 1:111–32 [Google Scholar]
  148. Smith EC, Denison MR. 148.  2012. Implications of altered replication fidelity on the evolution and pathogenesis of coronaviruses. Curr. Opin. Virol. 2:519–24 [Google Scholar]
  149. Eckerle LD, Becker MM, Halpin RA, Li K, Venter E. 149.  et al. 2010. Infidelity of SARS-CoV nsp14-exonuclease mutant virus replication is revealed by complete genome sequencing. PLOS Pathog. 6:e1000896Describes the relevance of coronavirus ExoN activity in replication fidelity and proofreading mechanisms. [Google Scholar]
  150. Eckerle LD, Lu X, Sperry SM, Choi L, Denison MR. 150.  2007. High fidelity of murine hepatitis virus replication is decreased in nsp14 exoribonuclease mutants. J. Virol. 81:12135–44 [Google Scholar]
  151. Bouvet M, Imbert I, Subissi L, Gluais L, Canard B, Decroly E. 151.  2012. RNA 3′-end mismatch excision by the severe acute respiratory syndrome coronavirus nonstructural protein nsp10/nsp14 exoribonuclease complex. PNAS 109:9372–77 [Google Scholar]
  152. Smith EC, Blanc H, Vignuzzi M, Denison MR. 152.  2013. Coronaviruses lacking exoribonuclease activity are susceptible to lethal mutagenesis: evidence for proofreading and potential therapeutics. PLOS Pathog. 9:e1003565 [Google Scholar]
  153. Donaldson EF, Sims AC, Graham RL, Denison MR, Baric RS. 153.  2007. Murine hepatitis virus replicase protein nsp10 is a critical regulator of viral RNA synthesis. J. Virol. 81:6356–68 [Google Scholar]
  154. Bouvet M, Lugari A, Posthuma CC, Zevenhoven JC, Bernard S. 154.  et al. 2014. Coronavirus nsp10, a critical co-factor for activation of multiple replicative enzymes. J. Biol. Chem. 289:25783–96 [Google Scholar]
  155. Decroly E, Ferron F, Lescar J, Canard B. 155.  2012. Conventional and unconventional mechanisms for capping viral mRNA. Nat. Rev. Microbiol. 10:51–65 [Google Scholar]
  156. Bouvet M, Debarnot C, Imbert I, Selisko B, Snijder EJ. 156.  et al. 2010. In vitro reconstitution of SARS-coronavirus mRNA cap methylation. PLOS Pathog. 6:e1000863 [Google Scholar]
  157. Nogales A, Márquez-Jurado S, Galán C, Enjuanes L, Almazan F. 157.  2012. Transmissible gastroenteritis coronavirus RNA-dependent RNA polymerase and nonstructural proteins 2, 3, and 8 are incorporated into viral particles. J. Virol. 86:1261–66Reports the incorporation of RTC components into coronavirus particles. [Google Scholar]
  158. Neuman BW, Joseph JS, Saikatendu KS, Serrano P, Chatterjee A. 158.  et al. 2008. Proteomics analysis unravels the functional repertoire of coronavirus nonstructural protein 3. J. Virol. 82:5279–94 [Google Scholar]
  159. Sims AC, Tilton SC, Menachery VD, Gralinski LE, Schafer A. 159.  et al. 2013. Release of severe acute respiratory syndrome coronavirus nuclear import block enhances host transcription in human lung cells. J. Virol. 87:3885–902 [Google Scholar]
  160. Moshynskyy I, Viswanathan S, Vasilenko N, Lobanov V, Petric M. 160.  et al. 2007. Intracellular localization of the SARS coronavirus protein 9b: evidence of active export from the nucleus. Virus Res. 127:116–21 [Google Scholar]
  161. Rowland RR, Kervin R, Kuckleburg C, Sperlich A, Benfield DA. 161.  1999. The localization of porcine reproductive and respiratory syndrome virus nucleocapsid protein to the nucleolus of infected cells and identification of a potential nucleolar localization signal sequence. Virus Res. 64:1–12 [Google Scholar]
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