Coronavirus Genome Structure and Replication

  • D. A. Brian
  • R. S. Baric
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 287)


In addition to the SARS coronavirus (treated separately elsewhere in this volume), the complete genome sequences of six species in the coronavirus genus of the coronavirus family [avian infectious bronchitis virus-Beaudette strain (IBV-Beaudette), bovine coronavirus-ENT strain (BCoV-ENT), human coronavirus-229E strain (HCoV-229E), murine hepatitis virus-A59 strain (MHV-A59), porcine transmissible gastroenteritis-Purdue 115 strain (TGEV-Purdue 115), and porcine epidemic diarrhea virus-CV777 strain (PEDV-CV777)] have now been reported. Their lengths range from 27,317 nt for HCoV-229E to 31,357 nt for the murine hepatitis virus-A59, establishing the coronavirus genome as the largest known among RNA viruses. The basic organization of the coronavirus genome is shared with other members of the Nidovirus order (the torovirus genus, also in the family Coronaviridae, and members of the family Arteriviridae) in that the nonstructural proteins involved in proteolytic processing, genome replication, and subgenomic mRNA synthesis (transcription) (an estimated 14–16 end products for coronaviruses) are encoded within the 5′-proximal two-thirds of the genome on gene 1 and the (mostly) structural proteins are encoded within the 3′-proximal one-third of the genome (8–9 genes for coronaviruses). Genes for the major structural proteins in all coronaviruses occur in the 5′ to 3′ order as S, E, M, and N. The precise strategy used by coronaviruses for genome replication is not yet known, but many features have been established. This chapter focuses on some of the known features and presents some current questions regarding genome replication strategy, the cis-acting elements necessary for genome replication [as inferred from defective interfering (DI) RNA molecules], the minimum sequence requirements for autonomous replication of an RNA replicon, and the importance of gene order in genome replication.


Infectious Bronchitis Virus Genome Replication Mouse Hepatitis Virus Murine Coronavirus Slippery Sequence 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adami C, Pooley J, Glomb J, Stecker E, Fazal F, Fleming JO, Baker SC (1995) Evolution of mouse hepatitis virus (MHV) during chronic infection: quasispecies nature of the persisting MHV RNA. Virology 209:337–346CrossRefPubMedGoogle Scholar
  2. Ahlquist P (2002) RNA-dependent RNA polymerases, viruses, and RNA silencing. Science 296:1270–1273CrossRefPubMedGoogle Scholar
  3. Almazan F, Gonzalez JM, Penzes Z, Izeta a, Calvo E, Plana-Duran J, Enjuanes L (2000) Engineering the largest RNA virus genome as an infectious bacterial artificial chromosome. Proc Natl Acad Sci USA 97:5516–5521CrossRefPubMedGoogle Scholar
  4. Baric RS, Nelson GW, Fleming JO, Deans RJ, Keck JG, Casteel N, Stohlman SA (1988) Interactions between coronavirus nucleocapsid protein and viral RNAs: implications for viral transcription. J. Virol 62:4280–4287PubMedGoogle Scholar
  5. Baric RS, Sullivan E, Hensley L, Yount B, Chen W (1999) Persistent infection promotes cross-species transmissibility of mouse hepatitis virus. J Virol 73:638–649PubMedGoogle Scholar
  6. Baric RS, Yount B (2000) Subgenomic negative-strand RNAs function during mouse hepatitis virus infection. J Virol 74:4039–4046CrossRefPubMedGoogle Scholar
  7. Barton DJ, Donnell BJO, Flanegan JB (2001) 5′ Cloverleaf in poliovirus RNA is a cis-acting replication element required for negative-strand synthesis. EMBO J 20:1439–1448CrossRefPubMedGoogle Scholar
  8. Bos ECW, Dobbe JC, Luytjes W, Spaan WJM (1997) A subgenomic mRNA transcript of the coronavirus mouse hepatitis virus strain A59 defective interfering (DI) RNA is packaged when it contains the DI RNA packaging signal. J Virol 71:5684–5687PubMedGoogle Scholar
  9. Boursnell MEG, Brown TDK, Foulds IJ, Green, PF, Tomley FM, Binns MM (1987) Completion of the sequence of the genome of the coronavirus avian infectious bronchitis virus. J Gen Virol 68:57–77PubMedGoogle Scholar
  10. Bredenbeek PJ, Pachuk CJ, Noten AFH, Charite, J, Luytjes W, Weiss SR, Spaan WJM (1990) The primary structure and expression of the second open reading frame of the polymerase gene of the coronavirus MHV-A59: a highly conserved polymerase is expressed by an efficient ribosomal frameshifting mechanism. Nucleic Acids Res 18:1825–1832PubMedGoogle Scholar
  11. Brian DA, Chang RY, Hofmann MA, Sethna PB (1994) Role of subgenomic minusstrand RNA in coronavirus replication. Arch Virol 9(Suppl): 173–180PubMedGoogle Scholar
  12. Brian DA, Dennis DE, Guy JS (1980) Genome of porcine transmissible gastroenteritis virus. J Virol 34:410–415PubMedGoogle Scholar
  13. Brian DA, Spaan WJM (1997) Recombination and coronavirus defective interfering RNAs. Semin Virol 8:101–111CrossRefGoogle Scholar
  14. Brierly I, Boursnell MEG, Binns MM, Bilimoria B, Blok VC, Brown TDK, Inglis SC (1987) An efficient ribosomal frame-shifting signal in the polymerase-encoding region of the coronavirus IBV. EMBO J 6:3779–3785PubMedGoogle Scholar
  15. Brierly I, Digard P, Inglis SC (1989) Characterization of an efficient coronavirus ribosomal frameshifting signal: requirement for an RNA pseudoknot. Cell 57:537–547CrossRefPubMedGoogle Scholar
  16. Brown TDK, Brierley I (1995) The coronavirus nonstructural proteins. In The Coronaviridae (S.G. Siddell, ed.), Plenum Press, New York and London, pp. 191–2171Google Scholar
  17. Casais R, Thiel V, Siddell SG, Cavanagh D, Britton P (2001) Reverse genetics system for the avian coronavirus infectious bronchitis virus. J Virol 75:12359–12369CrossRefPubMedGoogle Scholar
  18. Cavanagh D, Brian DA, Brinton MA, Enjuanes L, Holmes KV, Horzinek MC, Lai MMC, Laude H, Plagemann PGW, Siddell, SG, Spaan W, Taguchi F, Talbot PJ (1997) Nidovirales: a new order comprising Coronaviridae and Arteriviridae. Arch Virol. 142:629–633PubMedGoogle Scholar
  19. Chang RY, Brian DA (1996) Cis requirement for N-specific protein sequence in bovine coronavirus defective interfering RNA replication. J Virol 70:2201–2207PubMedGoogle Scholar
  20. Chang RY, Hofmann MA, Sethna PB, Brian BA (1994) A cis-acting function for the coronavirus leader in defective interfering RNA replication. J Virol 68:8223–8231PubMedGoogle Scholar
  21. Chang RY, Krishnan R, Brian DA (1996) The UCUAAAC promoter motif is not required for high-frequency leader recombination in bovine coronavirus defective interfering RNA. J Virol 70:2720–2729PubMedGoogle Scholar
  22. Chouljenko VN, Lin XQ, Storz J, Kousoulas KG, Gorbalenya AE (2001) Comparison of genomic and predicted amino acid sequences of respiratory and enteric bovine coronaviruses isolated from the same animal with fatal shipping pneumonia. J Gen Virol 82:2927–2933PubMedGoogle Scholar
  23. Cologna R, Hogue BG (2000) Identification of a bovine coronavirus packaging signal. J Virol 74:580–583PubMedGoogle Scholar
  24. Compton SR, Rogers DB, Holmes KV, Fertsch D, Remenick J, McGowan JJ (1987) In vitro replication of mouse hepatitis virus strain A59. J Virol 61:1814–1820PubMedGoogle Scholar
  25. Curtis K, Yount B, Baric RS (2002) Heterologous gene expression from transmissible gastroenteritis virus replicon particles. J Virol 76:1422–1434PubMedGoogle Scholar
  26. Dalton K, Casais R, Shaw K, Stirrups K, Evans S, Britton P, Brown TDK, Cavanagh, D (2001) cis-Acting sequences required for coronavirus infectious bronchitis virus defective-RNA replication and packaging. J Virol 75:125–133CrossRefPubMedGoogle Scholar
  27. de Groot RJ, van der Most RG, Spaan WJM (1992) The fitness of defective interfering murine coronavirus DI-a and its derivatives is decreased by nonsense and frame-shift mutations. J Virol 66:5898–5905PubMedGoogle Scholar
  28. de Haan CAM, Masters PS, Shen X, Weiss S, Rottier PJM (2002) The group-specific murine coronavirus genes are not essential, but their deletion, by reverse genetics, is attenuating in the natural host. Virology 296:177–189CrossRefPubMedGoogle Scholar
  29. Denison MR, Spaan WJ, van der Meer Y, Gibson CA, Sims AC, Prentice E, Lu XT (1999) The putative helicase of the coronavirus mouse hepatitis virus is processed from the replicase gene poly protein and localizes in complexes that are active in viral RNA synthesis. J Virol 73:6862–6871PubMedGoogle Scholar
  30. Dennis DE, Brian DA (1982) RNA-dependent RNA polymerase activity in coronavirus-infected cells. J Virol 42:153–164PubMedGoogle Scholar
  31. de Vries AAF, Horzinek MC, Rottier PJM, de Groot RJ (1997) The genome organization of the Nidovirales: similarities and differences between arteri-, toro-, and coronaviruses. Semin Virol 8:33–47CrossRefGoogle Scholar
  32. Egger D, Teterina N, Ehrenfeld E, Bienz K (2000) Formation of the poliovirus replication complex requires coupled viral translation, vesicle production, and viral RNA synthesis. J Virol 74:6570–6580CrossRefPubMedGoogle Scholar
  33. Eleouet JF, Rasschaert D, Lambert P, Levy L, Vende P, Laude H (1995) Complete sequence (20 kilobases) of the polyprotein-encoding gene 1 of transmissible gastroenteritis virus. Virology 206:817–822CrossRefPubMedGoogle Scholar
  34. Enjuanes L, Brian D, Cavanagh D, Holmes K, Lai MMC, Laude H, Masters P, Rottier PJM, Siddell SG, Spaan WJM, Taguchi F, Talbot P (2000) Coronaviridae. In: Virus Taxonomy, Seventh Report of the International Committee on Taxonomy of Viruses (MHV van Regenmortel, CM Fauquet, DHL Bishop, EB Carstens, MK Estes, SM Lemon, J Maniloff, MA Mayo, DJ McGeoch, CR Pringle, RB Wickner, eds) Academic Press, San Diego. pp 835–849Google Scholar
  35. Enjuanes L, Spaan WJM, Snijder E, Cavanagh D (2000) Nidovirales. In: Virus Taxonomy, Seventh Report of the International Committee on Taxonomy of Viruses (MHV van Regenmortel, CM Fauquet, DHL Bishop, EB Carstens, MK Estes, SM Lemon, J Maniloff, MA Mayo, DJ McGeoch, CR Pringle, RB Wickner, eds) Academic Press, San Diego. pp 827–834Google Scholar
  36. Escors D, Izeta A, Capiscol C, Enjuanes L (2003) Transmissible gastroenteritis coronavirus packaging signal is located at the 5'end of the virus genome. J Virol 77:7890–7902CrossRefPubMedGoogle Scholar
  37. Fosmire JA, Hwang K, Makino S (1992) identification and characterization of a coronavirus packaging signal. J Virol 66:3522–3530PubMedGoogle Scholar
  38. Frolov I, Hardy R, Rice CM (2001) Cis-acting RNA elements at the 5′ end of Sindbis virus genome RNA regulate minus-and plus-strand RNA synthesis. RNA 7:1638–1651CrossRefPubMedGoogle Scholar
  39. Gamarnik AV, Andino R (1998) Switch from translation to RNA replication in a positive-stranded RNA virus. Genes Dev 12:2293–2304PubMedGoogle Scholar
  40. Goebel SJ, Hsue B, Dombrowski TF, Masters PS (2004) Characterization of the RNA components of a putative molecular switch in the 3'untranstated region of the murine coronavirus. J Virol 78:669–682CrossRefPubMedGoogle Scholar
  41. Gosert R, Kanjanahaluethai A, Egger D, Bienz K, Baker SC (2002) RNA replication of mouse hepatitis virus takes place at double-membrane vesicles. J. Virol 76:3697–3708CrossRefPubMedGoogle Scholar
  42. Herold J, Andino R (2001) Poliovirus RNA replication requires genome circularization through a protein-protein bridge. Mol Cell 7:581–591CrossRefPubMedGoogle Scholar
  43. Herold J, Raabe T, Schelle-Prinz B, Siddell SG (1993) Nucleotide sequence of the human coronavirus 229E RNA polymerase locus. Virology 195:680–691CrossRefPubMedGoogle Scholar
  44. Herold, J, Siddell SG (1993) An “elaborated” pseudoknot is required for high frequency frameshifting during translation of HCV 229E polymerase mRNA. Nucleic Acids Res 21:5838–5842PubMedGoogle Scholar
  45. Hofmann MA, Brian DA (1991) The 5′ end of coronavirus minus-strand RNAs contains a short poly(U) tract. J Virol 65:6331–6333PubMedGoogle Scholar
  46. Hofmann MA, Sethna PB, Brian DA (1990) Bovine coronavirus mRNA replication continues throughout persistent infection in cell culture. J Virol 64:4108–4114PubMedGoogle Scholar
  47. Hsue B, Hartshorne T, Masters PS (2000) Characterization of an essential RNA secondary structure in the 3′ untranslated region of murine coronavirus genome. J Virol 74:6911–6921CrossRefPubMedGoogle Scholar
  48. Hsue B, Masters PS (1997) A bulged stem-loop structure in the 3′ untranslated region of the coronavirus mouse hepatitis virus genome is essential for replication. J Virol 71:7567–7578PubMedGoogle Scholar
  49. Huang P, Lai MMC (1999) Polypyrimidine tract-binding protein binds to the complementary strand of the mouse hepatitis virus 3′ untranslated region, thereby altering RNA conformation. J Virol 73:9110–9116PubMedGoogle Scholar
  50. Izeta A, Smerdou C, Alonso S., Penzes Z, Mendez A, Plana-Duran J, Enjuanes, L (1999) Replication and packaging of transmissible gastroenteritis coronavirus-derived synthetic minigenomes. J Virol 73:1535–1545PubMedGoogle Scholar
  51. Jengrach M, Thiel V, Siddell S (1999) Characterization of an internal ribosome entry site within mRNA 5 of murine hepatitis virus. Arch Virol 144:921–933CrossRefPubMedGoogle Scholar
  52. Khromykh AA, Sedlak PL, Westaway EG (1999) Trans-complementation analysis of the flavivirus Kunjin ns5 gene reveals an essential role for translation of its N-terminal half in RNA replication. J Virol 73:9247–9255PubMedGoogle Scholar
  53. Kim KH, Makino S (1995) Two murine coronavirus genes suffice for viral RNA synthesis. J Virol 69:2313–2321PubMedGoogle Scholar
  54. Kim Y, Makino S (1995) Characterization of a murine coronavirus defective interfering RNA internal cis-acting replication signal. J Virol 69:4963–4971PubMedGoogle Scholar
  55. Kim YN, Jeong YS, Makino S (1993) Analysis of cis-acting sequences essential for coronavirus defective interfering RNA replication. Virology 197:53–63CrossRefPubMedGoogle Scholar
  56. Kim YN, Lai MMC, Makino S (1993) Generation and selection of coronavirus defective interfering RNA with large open reading frames by RNA recombination and possible editing. Virology 194:244–253CrossRefPubMedGoogle Scholar
  57. Kocherhans R. Bridgen A, Ackermann M, Tobler K (2001) Completion of the porcine epidemic diarrhoea coronavirus (PEDV) genome sequence. Virus Genes 23:137–144CrossRefPubMedGoogle Scholar
  58. Kozak M (1991) Structural features in eukaryotic mRNAs that modulate the initiation of translation. J Biol Chem 266:19867–19870PubMedGoogle Scholar
  59. Lai MMC, Cavanagh D (1997) The molecular biology of coronaviruses. Adv Virus Res 48:1–100CrossRefPubMedGoogle Scholar
  60. Lai MMC, Holmes KC (2001) Coronaviridae: the viruses and their replication. In Fields Virology, Fourth Edition (Knipe DM, Howley PM, eds), Lippincott Williams and Wilkins, Philadelphia, pp. 1163–1185Google Scholar
  61. Lai MMC, Patton CD, Stohlman SA (1982) Further characterization of mRNAs of mouse hepatitis virus: presence of common 5′-end nucleotides. J Virol 41:557–565PubMedGoogle Scholar
  62. Laude H, Masters PS (1995) The coronavirus nucleocapsid protein. In The Coronaviridae (S.G. Siddell, ed.), Plenum Press, New York and London, pp. 141–163Google Scholar
  63. Leparc-Goffart I, Hingley ST, Chua MM, Jiang X, Lavi E, Weiss SR (1997) Altered pathogenesis of a mutant of the murine coronavirus MHV-A59 is associated with a Q159L amino acid substitution in the spike protein. Virology 239:1–10CrossRefPubMedGoogle Scholar
  64. Levis R, Weiss BG, Tsiang M, Huang H, Schlesinger S (1986) Deletion mapping of Sindbis virus DI RNAs derived from cDNAs defines the sequences essential for replication and packaging. Cell 44:137–145CrossRefPubMedGoogle Scholar
  65. Li HP, Huang P, Park S, Lai MMC (1999) Polypyrimidine tract-binding protein binds to the leader RNA of mouse hepatitis virus and serves as a regulator of viral transcription. J Virol 73:772–777PubMedGoogle Scholar
  66. Li HP, Zhang X, Duncan R, Comai L, Lai MMC (1997) Heterogeneous nuclear ribonucleoprotein A1 binds to the transcription-regulatory region of mouse hepatitis virus RNA. Proc Natl Acad Sci USA 94:9544–9549CrossRefPubMedGoogle Scholar
  67. Li X, Palese P (1992) Mutational analysis of the promoter required for influenza virus virion RNA synthesis. J Virol 66:4331–4338PubMedGoogle Scholar
  68. Liao CL, Lai MMC (1995) A cis-acting viral protein is not required for the replication of a coronavirus defective interfering RNA. Virology 209:428–436CrossRefPubMedGoogle Scholar
  69. Lin Y, Lai MMC (1993) Deletion mapping of a mouse hepatitis virus defective interfering RNA reveals the requirement of an internal and discontiguous sequence for replication. J Virol 67:6110–6118PubMedGoogle Scholar
  70. Lin YJ, Liao CL, Lai MMC (1994) Identification of the cis-acting signal for minus-strand RNA synthesis of a murine coronavirus: implications for the role of minus-strand RNA in RNA replication and transcription. J Virol 68:8131–8140PubMedGoogle Scholar
  71. Liu DX, Inglis SC (1992) Internal entry of ribosomes on a tricistronic mRNA encoded by infectious bronchitis virus. J Virol 66:6143–6154PubMedGoogle Scholar
  72. Liu Q, Johnson RF, Leibowitz JL (2001) Secondary structural elements within the 3′ untranslated region of mouse hepatitis virus strain JHM genomic RNA. J Virol 75:12105–12113CrossRefPubMedGoogle Scholar
  73. Liu Q, Yu W, Leibowitz JL (1997) A specific host cellular protein binding element near the 3′ end of mouse hepatitis genomic RNA. Virology 232:74–85CrossRefPubMedGoogle Scholar
  74. Luytjes W (1995) Coronavirus gene expression. In The Coronaviridae (S.G. Siddell, ed.), Plenum Press, New York and London, pp. 33–54Google Scholar
  75. Luytjes W, Gerritsma H, Spaan WJ (1996) Replication of synthetic defective interfering RNAs derived from coronavirus mouse hepatitis virus-A59. Virology 216:174–183CrossRefPubMedGoogle Scholar
  76. Makino S, Fujioka N, Fujiwara K (1985) Structure of the intracellular defective viral RNAs of defective interfering particles of mouse hepatitis virus. J Virol 54:329–336PubMedGoogle Scholar
  77. Makino S, Joo M, Makino JK (1991) A system for study of coronavirus mRNA synthesis: a regulated, expressed subgenomic defective interfering RNA results from intergenic site insertion. J Virol 65:6031–6041PubMedGoogle Scholar
  78. Makino S, Lai MMC (1989) High-frequency leader sequence switching during coronavirus defective interfering RNA replication. J Virol 63:5285–5292PubMedGoogle Scholar
  79. Makino S, Shieh CK, Keck JG, Lai MMC (1988) Defective interfering particles of murine coronavirus: mechanism of synthesis of defective viral RNAs. Virology 163:104–111CrossRefPubMedGoogle Scholar
  80. Makino S, Shieh CK, Soe LH, Baker SC, Lai MMC (1988) Primary structure and translation of a defective interfering RNA of murine coronavirus. Virology 166:1–11CrossRefPubMedGoogle Scholar
  81. Makino S, Yokomori K, Lai MMC (1990) Analysis of efficiently packaged defective interfering RNAs of murine coronavirus: localization of a possible RNA-packaging signal. J Virol 64:6045–6053PubMedGoogle Scholar
  82. Masters PS (1999) Reverse genetics of the largest RNA viruses. Adv Virus Res 53:245–264PubMedGoogle Scholar
  83. Masters PS, Koetzner CA, Kerr CA, Heo Y (1994) Optimization of targeted RNA recombination and mapping of a novel nucleocapsid gene mutation in the coronavirus mouse hepatitis virus. J Virol 68:328–337PubMedGoogle Scholar
  84. Mendez A, Smerdou C, Izeta A, Gebauer F, Enjuanes L (1996) Molecular characterization of transmissible gastroenteritis coronavirus defective interfering genomes: packaging and heterogeneity. Virology 217:495–507CrossRefPubMedGoogle Scholar
  85. Molenkamp R, van Tol H, Rozier BCD, van der Meer Y, Spaan WJM, Snijder EJ (2000) The arterivirus replicase is the only viral protein required for genome replication and subgenomic mRNA transcription. J Gen Virol 81:2491–2496PubMedGoogle Scholar
  86. Molla A, Paul AV, Wimmer E (1991) Cell-free, de novo synthesis of poliovirus. Science 254:1647–1651PubMedGoogle Scholar
  87. Morris DR, Geballe AP (2000) Upstream open reading frames as regulators of mRNA translation. Mol Cell Biol 20:8635–8642CrossRefPubMedGoogle Scholar
  88. Nanda SK, Leibowitz JL (2001) Mitochondrial aconitase binds to the 3′ untranslated region of the mouse hepatitis virus genome. J Virol75:3352–3362CrossRefPubMedGoogle Scholar
  89. Narayanan K, Chen C-J, Maeda J, Makino S (2003) Nucleocapsid-independent specific viral RNA packaging via viral envelope protein and viral RNA signal. J Virol 77:2922–2927CrossRefPubMedGoogle Scholar
  90. Narayanan K, Makino S (2001) Cooperation of an RNA packaging signal and a viral envelope protein in coronavirus RNA packaging. J Virol 75:9059–9067CrossRefPubMedGoogle Scholar
  91. Nelson GW, Stohlman SA, Tahara SM (2000) High affinity interaction between nucleocapsid protein and leader/intergenic sequence of mouse hepatitis virus RNA. J Gen Virol 81:181–188PubMedGoogle Scholar
  92. Novak JE, Kirkegaard K (1991) Improved method for detecting poliovirus negative strands used to demonstrate specificity of positive-strand encapsidation and the ratio of positive to negative strands in infected cells. J Virol 65:3384–3387PubMedGoogle Scholar
  93. Okumura A, Machii K, Azuma S, Toyoda Y, Kyuwa S (1996) Maintenance of pluripotency in mouse embryonic stem cells persistently infected with murine coronavirus. J Virol 70:4146–4149PubMedGoogle Scholar
  94. Penzes Z, Gonzalez JM, Calvo E, Izeta A, Smerdou C, Mendez A, Sanchez CM, Sola I, Almazan F, Enjuanes L (2001) Complete genome sequence of transmissible gastroenteritis coronavirus PUR46-MAD clone and evolution of the Purdue virus cluster. Virus Genes 23:105–118CrossRefPubMedGoogle Scholar
  95. Penzes Z, Tibbles K, Shaw K, Britton P, Brown TDK, Cavanagh D (1994) Characterization of a replicating and packaged defective RNA of avian coronavirus infectious bronchitis virus. Virology 203:286–293CrossRefPubMedGoogle Scholar
  96. Penzes Z, Wroe C, Brown TDK, Britton P, Cavanagh D (1996) Replication and packaging of coronavirus infectious bronchitis virus defective RNAs lacking a long open reading frame. J Virol 70:8660–8668PubMedGoogle Scholar
  97. Raman S, Bouma P, Williams GD, Brian DA (2003) Stem-loop III in the 5′ UTR is a cis-acting element in bovine coronavirus DI RNA replication. J Virol in pressGoogle Scholar
  98. Repass JF, Makino S (1998) Importance of the positive-strand RNA secondary structure of a murine coronavirus defective interfering RNA internal replication signal in positive-strand RNA synthesis. J Virol 72:7926–7933PubMedGoogle Scholar
  99. Sarma JD, Hingley ST, Lai MMC, Weiss SR, Lavi E (1999) Direct submission to Gen-Bank.Google Scholar
  100. Sawicki SG, Sawicki DL (1990) Coronavirus transcription: subgenomic mouse hepatitis virus replicative intermediates function in mRNA synthesis. J Virol 64:1050–1056PubMedGoogle Scholar
  101. Sawicki SG, Sawicki DL (1995) Coronaviruses use discontinuous extension for synthesis of subgenome-length negative strands. Adv Exp Med Biol 380:499–506PubMedGoogle Scholar
  102. Sawicki SG, Sawicki DL (1998) A new model for coronavirus transcription. Adv Exp Med Biol 280:215–218.Google Scholar
  103. Sawicki DL, Wang T, Sawicki SG (2001) The RNA structures engaged in replication and transcription of the A59 strain of mouse hepatitis virus. J Gen Virol 82:385–396PubMedGoogle Scholar
  104. Schaad MC, Baric RS (1994) Genetics of mouse hepatitis virus transcription: evidence that subgenomic negative strands are functional templates. J Virol 68:8169–8179PubMedGoogle Scholar
  105. Schochetman G, Stevens RH, Simpson RW (1977) Presence of infectious polyadenylated RNA in the coronavirus avian bronchitis virus. Virology 77:772–782CrossRefPubMedGoogle Scholar
  106. Senanayake SD, Brian DA (1999) Translation from the 5′ UTR of mRNA 1 is repressed, but that from the 5′ UTR of mRNA 7 is stimulated in coronavirus-infected cells. J Virol 73:8003–8009PubMedGoogle Scholar
  107. Sethna PB, Brian DA (1997) Coronavirus subgenomic and genomic minus-strand RNAs copartition in membrane-protected replication complexes. J Virol 71:7744–7749PubMedGoogle Scholar
  108. Sethna PB, Hofmann MA, Brian DA (1991) Minus-strand copies of replicating coronavirus mRNAs contain antileaders. J Virol 65:320–325PubMedGoogle Scholar
  109. Sethna, PB, Hung SL, Brian DA (1989) Coronavirus subgenomic minus-strand RNA and the potential for mRNA replicons. Proc Natl Acad Sci USA 86:5626–5630PubMedGoogle Scholar
  110. Shi ST, Schiller JJ, Kanjanahaluethai, A, Baker SC, Oh JW, Lai MMC (1999) Colocalization and membrane association of murine hepatitis virus gene 1 products and de novo-synthesized viral RNA in infected cells. J Virol 73:5957–5969PubMedGoogle Scholar
  111. Siddell, SG (1995) The Coronaviridae. In The Coronaviridae (S.G. Siddell, ed.), Plenum Press, New York and London, pp. 1–10Google Scholar
  112. Snijder EJ, Meulenberg JJM (1998) The molecular biology of arteriviruses. J Gen Virol 79:961–979PubMedGoogle Scholar
  113. Spagnolo JF, Hogue BG (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 74:5053–5065CrossRefPubMedGoogle Scholar
  114. Stirrups K, Shaw K, Evans S, Dalton K, Cananagh D, Britton P (2000) Leader switching occurs during the rescue of defective RNAs by heterologous strains of the coronavirus infectious bronchitis virus. J Gen Virol 81:791–801PubMedGoogle Scholar
  115. Stohlman SA, Baric RS, Nelson GN, Soe LH, Welter LM, Deans RJ (1988) Specific interactions between coronavirus leader RNA and nucleocapsid protein. J Virol 62:4288–4295PubMedGoogle Scholar
  116. Stohlamn SA, Bergmann CC, Perlman S (1999) Selected animal models of viral persistence: mouse hepatitis virus. In Persistent Viral Infections (Ahmed R, Chen ISY, eds) John Wiley and Sons, New York, pp. 537–557Google Scholar
  117. Tahara SM, Dietlin TA, Nelson GW, Stohlman SA, Manno DJ (1998) Translation effector properties of mouse hepatitis virus nucleocapsid protein. Adv Exp Med Biol 440:313–318PubMedGoogle Scholar
  118. Thiel V, Herold J, Schelle B, Siddell SG (2001) Infectious RNA transcribed in vitro from a cDNA copy of the human coronavirus genome cloned in vaccinia virus. J Gen Virol 82:1273–1281PubMedGoogle Scholar
  119. Thiel V, Herold J, Schelle B, Siddell SG (2001) Viral replicase gene products suffice for coronavirus discontinuous transcription. J Virol 75:6676–6681CrossRefPubMedGoogle Scholar
  120. Thiel V, Siddell SG (1994) Internal ribosomal entry in the coding region of murine hepatitis virus mRNA 5. J Gen Virol 75:3041–3046PubMedGoogle Scholar
  121. van der Meer Y, Snijder EJ, Dobbe JC, Schleich S, Denison MR, Spaan WJ, Locker JK (1999) Localization of mouse hepatitis virus nonstructural proteins and RNA synthesis indicates a role for late endosomes in viral replication. J Virol 73:7641–7657.PubMedGoogle Scholar
  122. van der Most RG, Bredenbeek PJ, Spaan WJM (1991) A domain at the 3′ end of the polymerase gene is essential for encapsidation of coronavirus defective interfering RNAs. J Virol 65:3219–3226PubMedGoogle Scholar
  123. van der Most RG, Luytjes W, Rutjes S, Spaan WJM (1995) Translation but not the encoded sequence is essential for the efficient propagation of the defective interfering RNAs of the coronavirus mouse hepatitis virus. J Virol 69:3744–3751PubMedGoogle Scholar
  124. van der Most RG, Spaan WJM (1995) Coronavirus replication, transcription, and RNA recombination. In The Coronaviridae (S.G. Siddell, ed.), Plenum Press, New York and London, pp. 11–31Google Scholar
  125. van Marle G, van Dinten LC, Spaan WJM, Luytjes W, Snijder EJ (1999) Characterization of an equine arteritis virus replicase mutant defective in subgenomic mRNA synthesis. J Virol 73:5274–5281PubMedGoogle Scholar
  126. Williams AK, Wang L, Sneed LW, Collisson EW (1993) Analysis of a hypervariable region in the 3′ non-coding end of the infectious bronchitis virus genome. Virus Res 28:19–27CrossRefPubMedGoogle Scholar
  127. Williams GD, Chang RY, Brian DA (1999) A phylogenetically conserved hairpin-type 3′ untranslated region pseudoknot functions in coronavirus RNA replication. J Virol 73:8349–8355PubMedGoogle Scholar
  128. Woo K, Joo M, Narayanan K, Kim KH, Makino S (1997) Murine coronavirus packaging signal confers packaging to nonviral RNA. J Virol 71:824–827PubMedGoogle Scholar
  129. Wu HY, Guy JS, Yoo D, Vlasak R, Urbach E, Brian DA (2003) Common RNA replication signals exist among group 2 coronaviruses: evidence for in vivo recombination between animal and human coronavirus molecules. Virology 315:174–183CrossRefPubMedGoogle Scholar
  130. Yoo D, Pei Y (2001) Full-length genomic sequence of bovine coronavirus (31 kb). Adv Exp Med Biol 494:73–76PubMedGoogle Scholar
  131. You S, Falgout B, Markoff L, Padmanabhan R (2001) In vitro RNA synthesis from exogenous dengue viral RNA templates requires long range interactions between 5′-and 3′-terminal regions that influence RNA structure. J Biol Chem 276:15581–15591CrossRefPubMedGoogle Scholar
  132. Yount B, Curtis KM, Baric RS (2000) Strategy for systematic assembly of large RNA and DNA genomes: the transmissible gastroenteritis virus model. J Virol 74:10600–19611CrossRefPubMedGoogle Scholar
  133. Yount B, Denison MR, Weiss SR, Baric RS (2002) Systematic assembly of a full-length infectious cDNA of mouse hepatitis virus strain A59. J Virol 76:11065–11078CrossRefPubMedGoogle Scholar
  134. Yu W, Leibowitz JL (1995) Specific binding of host cellular proteins to multiple sites within the 3′ end of mouse hepatitis virus genomic RNA. J Virol 69:2016–2023PubMedGoogle Scholar
  135. Zhang X, Lai MMC (1996) A 5′-proximal RNA sequence of murine coronavirus as a potential initiation site for genomic-length mRNA transcription. J Virol 70:705–711PubMedGoogle Scholar
  136. Zhao S, Shaw K, Cavanagh D (1993) Presence of subgenomic mRNAs in virions of coronavirus IBV. Virology 196:172–178CrossRefPubMedGoogle Scholar
  137. Ziebuhr J, Snijder EJ, Gorbalenya AE (2000) Virus-encoded proteinases and proteolytic processing in the Nidovirales. J Gen Virol 81:853–879PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • D. A. Brian
    • 1
  • R. S. Baric
    • 2
    • 3
  1. 1.Departments of Microbiology and PathobiologyUniversity of Tennessee, College of Veterinary MedicineKnoxvilleUSA
  2. 2.Department of Microbiology and Immunology, School of MedicineUniversity of North CarolinaChapel HillUSA
  3. 3.Department of Epidemiology, Program of Infectious Diseases, School of Public HealthUniversity of North CarolinaChapel HillUSA

Personalised recommendations