Chapter 23 : Coronaviruses and Arteriviruses

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Coronaviruses and Arteriviruses, Page 1 of 2

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This chapter summarizes the interactions of coronaviruses and arteriviruses with the innate immune response, including the type I interferon (IFN) system; and the strategies employed by these viruses to evade or inhibit the antiviral IFN response. Coronaviruses and arteriviruses are a group of enveloped animal RNA viruses that are united in the order . Very little is known about the inhibition of the type I IFN pathway by arteriviruses, while significant advances have been made, primarily using MHV and SARS-CoV, toward understanding how coronaviruses evade type I IFN induction and the type I IFN signaling pathway. Devaraj et al. showed that the papain-like protease (PLpro) domain of the SARS-CoV replicase protein, nsp3, one of the gene 1 proteins, is an IFN antagonist. In this report, using a plasmid-based expression system, the authors showed that PLpro interacts with IRF3 and inhibits its phosphorylation and nuclear translocation, thereby affecting the downstream activation of the type I IFN gene. Some studies have shown that coronaviruses employ posttranscriptional strategies to suppression general host gene expression in infected cells. The availability of transgenic and other valuable natural mouse models for MHV, SARS-CoV, and HCoV-229E enables researchers to investigate the role of nonstructural and accessory proteins in virulence and pathogenesis. Using such systems, the potential identification of some common, evolutionarily conserved molecular mechanisms of immune evasion among different groups of coronaviruses is an exciting possibility in the future.

Citation: Narayanan K, Makino S. 2009. Coronaviruses and Arteriviruses, p 373-387. In Brasier A, García-Sastre A, Lemon S (ed), Cellular Signaling and Innate Immune Responses to RNA Virus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555815561.ch23

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Porcine reproductive and respiratory syndrome virus
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Figure 1

Simplified scheme of the type I IFN activation and signaling pathways and their inhibition by coronaviruses. Internalization of RNA viruses exposes the genomic RNA to cytoplasmic RNA sensors like RIG-I, MDA-5, and LGP2 that recognize dsRNA and 5′-triphosphate ssRNA produced during the life cycle of RNA viruses. In the endosomes, RNA sensors like TLR3 and TLR7/8 recognize dsRNA and ssRNA, respectively. TLR3 and TLR7/8 signal through the adaptor proteins TRIF and MyD88, respectively, to activate IFN-α/β production. RIG-I and MDA-5 trigger signaling cascades via IPS-1, an adaptor protein on mitochondrial membrane, to activate IRF3, leading to IFN-β gene expression and production of IFN-β protein. The released IFN-α/β proteins bind to the cognate type I IFN receptors in the same cell or neighboring cells to activate a Stat-dependent pathway to trigger the induction of ISGs with ISRE promoter sequences. The different steps in the IFN activation and signaling pathways that are inhibited or targeted by coronaviral proteins, as discussed in the text, are indicated. IKK, Ikappa B kinase; IRAK, IL-1 receptor-associated; TBK, TANK (TRAF family member-associated NF-κB activator)-binding kinase; TRAF, tumor necrosis factor (TNF) receptor-associated factor.

Citation: Narayanan K, Makino S. 2009. Coronaviruses and Arteriviruses, p 373-387. In Brasier A, García-Sastre A, Lemon S (ed), Cellular Signaling and Innate Immune Responses to RNA Virus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555815561.ch23
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Image of Figure 2
Figure 2

Genome organization of selected members in the and families. The replicase ORFs, ORF1a and ORF1b, and the names of the major virion structural genes are indicated. The accessory genes are shown as black boxes. The figure is not drawn to scale. EAV, equine arteritis virus; RFS, ribosomal frameshift.

Citation: Narayanan K, Makino S. 2009. Coronaviruses and Arteriviruses, p 373-387. In Brasier A, García-Sastre A, Lemon S (ed), Cellular Signaling and Innate Immune Responses to RNA Virus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555815561.ch23
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Figure 3

Schematic representation of the nidovirus life cycle. Virus entry is triggered by attachment to the cellular receptor and fusion of the viral envelope to the plasma membrane or the endosomes, which releases the viral genome into the cytoplasm. The genome is translated to produce precursor polyproteins, pp1a and pp1ab, which are proteolytically processed to produce mature viral proteins necessary for replication and transcription. The replication machinery, localized on DMVs, produces the viral genomic RNA, minus-strand RNAs, and subgenomic mRNAs. Viral mRNAs are translated to produce proteins that undergo modifications in cellular compartments like ER/Golgi. Viral assembly and budding occurs on an ER/Golgi intermediate compartment (ERGIC), where the viral envelope proteins and viral RNPs are assembled into virus particles. The mature virus particles are exported in vesicles to the cell surface and released into the extracellular environment by fusion with the cell membrane. (Adapted from Fig. 6 in reference .)

Citation: Narayanan K, Makino S. 2009. Coronaviruses and Arteriviruses, p 373-387. In Brasier A, García-Sastre A, Lemon S (ed), Cellular Signaling and Innate Immune Responses to RNA Virus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555815561.ch23
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1. Aaronson, D. S.,, and, C. M. Horvath. 2002. A road map for those who don’t know JAK-Stat. Science 296:16531655.
2. Aich, P.,, H. L. Wilson,, R. S. Kaushik,, A. A. Potter,, L. A. Babiuk, and, P. Griebel. 2007. Comparative analysis of innate immune responses following infection of newborn calves with bovine rotavirus and bovine coronavirus. J. Gen. Virol. 88:27492761.
3. Akira, S., and, H. Hemmi. 2003. Recognition of pathogen-associated molecular patterns by TLR family. Immunol. Lett. 85:8595.
4. Almazan, F.,, M. L. Dediego,, C. Galan,, D. Escors,, E. Alvarez,, J. Ortego,, I. Sola,, S. Zuniga,, S. Alonso,, J. L. Moreno,, A. Nogales,, C. Capiscol, and, L. Enjuanes. 2006. Construction of a severe acute respiratory syndrome coronavirus infectious cDNA clone and a replicon to study coronavirus RNA synthesis. J. Virol. 80:1090010906.
5. Ank, N.,, H. West,, C. Bartholdy,, K. Eriksson,, A. R. Thomsen, and, S. R. Paludan. 2006. Lambda interferon (IFN-lambda), a type III IFN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo. J. Virol. 80:45014509.
6. Ank, N.,, H. West, and, S. R. Paludan. 2006. IFN-lambda: novel antiviral cytokines. J. Interferon Cytokine Res. 26:373379.
7. Balasuriya, U. B., and, N. J. MacLachlan. 2004. The immune response to equine arteritis virus: potential lessons for other arteriviruses. Vet. Immunol. Immunopathol. 102:107129.
8. Baudoux, P.,, L. Besnardeau,, C. Carrat,, P. Rottier,, B. Charley, and, H. Laude. 1998. Interferon alpha inducing property of coronavirus particles and pseudoparticles. Adv. Exp. Med. Biol. 440:377386.
9. Baudoux, P.,, C. Carrat,, L. Besnardeau,, B. Charley, and, H. Laude. 1998. Coronavirus pseudoparticles formed with recombinant M and E proteins induce alpha interferon synthesis by leukocytes. J. Virol. 72:86368643.
10. Brian, D. A., and, R. S. Baric. 2005. Coronavirus genome structure and replication. Curr. Top. Microbiol. Immunol. 287:130.
11. Brockway, S. M.,, C. T. Clay,, X. T. Lu, and, M. R. Denison. 2003. Characterization of the expression, intra-cellular localization, and replication complex association of the putative mouse hepatitis virus RNA-dependent RNA polymerase. J. Virol. 77:1051510527.
12. Cameron, M. J.,, L. Ran,, L. Xu,, A. Danesh,, J. F. BermejoMartin,, C. M. Cameron,, M. P. Muller,, W. L. Gold,, S. E. Richardson,, S. M. Poutanen,, B. M. Willey,, M. E. DeVries,, Y. Fang,, C. Seneviratne,, S. E. Bosinger,, D. Persad,, P. Wilkinson,, L. D. Greller,, R. Somogyi,, A. Humar,, S. Keshavjee,, M. Louie,, M. B. Loeb,, J. Brunton,, A. J. McGeer, and, D. J. Kelvin. 2007. Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome. J. Virol. 81:86928706.
13. Castilletti, C.,, L. Bordi,, E. Lalle,, G. Rozera,, F. Poccia,, C. Agrati,, I. Abbate, and, M. R. Capobianchi. 2005. Coordinate induction of IFN-alpha and -gamma by SARS-CoV also in the absence of virus replication. Virology 341:163169.
14. Cavanagh, D. 1997. Nidovirales: a new order comprising Coronaviridae and Arteriviridae. Arch. Virol. 142:629633.
15. Cella, M.,, D. Jarrossay,, F. Facchetti,, O. Alebardi,, H. Nakajima,, A. Lanzavecchia, and, M. Colonna. 1999. Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nat. Med. 5:919923.
16. Cervantes-Barragan, L.,, R. Zust,, F. Weber,, M. Spiegel,, K. S. Lang,, S. Akira,, V. Thiel, and, B. Ludewig. 2007. Control of coronavirus infection through plasmacytoid dendritic-cell-derived type I interferon. Blood 109:11311137.
17. Charley, B., and, H. Laude. 1988. Induction of alpha interferon by transmissible gastroenteritis coronavirus: role of transmembrane glycoprotein E1. J. Virol. 62:811.
18. Charley, B.,, S. Riffault, and, K. Van Reeth. 2006. Porcine innate and adaptative immune responses to influenza and coronavirus infections. Ann. N. Y. Acad. Sci. 1081:130136.
19. Cheung, C. Y.,, L. L. Poon,, I. H. Ng,, W. Luk,, S. F. Sia,, M. H. Wu,, K. H. Chan,, K. Y. Yuen,, S. Gordon,, Y. Guan, and, J. S. Peiris. 2005. Cytokine responses in severe acute respiratory syndrome coronavirus-infected macrophages in vitro: possible relevance to pathogenesis. J. Virol. 79:78197826.
20. Chinsangaram, J.,, M. E. Piccone, and, M. J. Grubman. 1999. Ability of foot-and-mouth disease virus to form plaques in cell culture is associated with suppression of alpha/beta interferon. J. Virol. 73:98919898.
21. Chung, H. K.,, J. H. Lee,, S. H. Kim, and, C. Chae. 2004. Expression of interferon-alpha and Mx1 protein in pigs acutely infected with porcine reproductive and respiratory syndrome virus (PRRSV). J. Comp. Pathol. 130:299305.
22. Cinatl, J.,, B. Morgenstern,, G. Bauer,, P. Chandra,, H. Rabenau, and, H. W. Doerr. 2003. Treatment of SARS with human interferons. Lancet 362:293294.
23. Colonna, M.,, G. Trinchieri, and, Y. J. Liu. 2004. Plasmacytoid dendritic cells in immunity. Nat. Immunol. 5:12191226.
24. de Lang, A.,, T. Baas,, T. Teal,, L. M. Leijten,, B. Rain,, A. D. Osterhaus,, B. L. Haagmans, and, M. G. Katze. 2007. Functional genomics highlights differential induction of antiviral pathways in the lungs of SARS-CoV-infected macaques. PLoS Pathog. 3:e112.
25. Devaraj, S. G.,, N. Wang,, Z. Chen,, Z. Chen,, M. Tseng,, N. Barretto,, R. Lin,, C. J. Peters,, C. T. Tseng,, S. C. Baker, and, K. Li. 2007. Regulation of IRF3-dependent innate immunity by the papain-like protease domain of the severe acute respiratory syndrome coronavirus. J. Biol. Chem. 282:3220832221.
26. Diebold, S. S.,, M. Montoya,, H. Unger,, L. Alexopoulou,, P. Roy,, L. E. Haswell,, A. Al-Shamkhani,, R. Flavell,, P. Borrow, and, C. Reis e Sousa. 2003. Viral infection switches non-plasmacytoid dendritic cells into high interferon producers. Nature 424:324328.
27. Drosten, C.,, S. Gunther,, W. Preiser,, S. van der Werf,, H. R. Brodt,, S. Becker,, H. Rabenau,, M. Panning,, L. Kolesnikova,, R. A. Fouchier,, A. Berger,, A. M. Burguiere,, J. Cinatl,, M. Eickmann,, N. Escriou,, K. Grywna,, S. Kramme,, J. C. Manuguerra,, S. Muller,, V. Rickerts,, M. Sturmer,, S. Vieth,, H. D. Klenk,, A. D. Osterhaus,, H. Schmitz, and, H. W. Doerr. 2003. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N. Engl. J. Med. 348:19671976.
28. Ferran, M. C., and, J. M. Lucas-Lenard. 1997. The vesicular stomatitis virus matrix protein inhibits transcription from the human beta interferon promoter. J. Virol. 71:371377.
29. Frieman, M.,, M. Heise, and, R. Baric. 2008. SARS coronavirus and innate immunity. Virus Res. 133:101112.
30. Frieman, M.,, B. Yount,, M. Heise,, S. A. KopeckyBromberg,, P. Palese, and, R. S. Baric. 2007. Severe acute respiratory syndrome coronavirus ORF6 antagonizes Stat1 function by sequestering nuclear import factors on the rough endoplasmic reticulum/Golgi membrane. J. Virol. 81:98129824.
31. Garlinghouse, L. E., Jr.,, A. L. Smith, and, T. Holford. 1984. The biological relationship of mouse hepatitis virus (MHV) strains and interferon: in vitro induction and sensitivities. Arch. Virol. 82:1929.
32. Glass, W. G.,, K. Subbarao,, B. Murphy, and, P. M. Murphy. 2004. Mechanisms of host defense following severe acute respiratory syndrome-coronavirus (SARSCoV) pulmonary infection of mice. J. Immunol. 173:40304039.
33. Goldsmith, C. S.,, K. M. Tatti,, T. G. Ksiazek,, P. E. Rollin,, J. A. Comer,, W. W. Lee,, P. A. Rota,, B. Bankamp,, W. J. Bellini, and, S. R. Zaki. 2004. Ultrastructural characterization of SARS coronavirus. Emerg. Infect. Dis. 10:320326.
34. Goodbourn, S.,, L. Didcock, and, R. E. Rndall. 2000. Interferons: cell signalling, immune modulation, antiviral response and virus countermeasures. J. Gen. Virol. 81:23412364.
35. Gosert, R.,, A. Kanjanahaluethai,, D. Egger,, K. Bienz, and, S. C. Baker. 2002. RNA replication of mouse hepatitis virus takes place at double-membrane vesicles. J. Virol. 76:36973708.
36. Grandvaux, N.,, B. R. tenOever,, M. J. Servant, and, J. Hiscott. 2002. The interferon antiviral response: from viral invasion to evasion. Curr. Opin. Infect. Dis. 15:259267.
37. Haagmans, B. L.,, T. Kuiken,, B. E. Martina,, R. A. Fouchier,, G. F. Rimmelzwaan,, G. van Amerongen,, D. van Riel,, T. de Jong,, S. Itamura,, K. H. Chan,, M. Tashiro, and, A. D. Osterhaus. 2004. Pegylated interferon-alpha protects type 1 pneumocytes against SARS coronavirus infection in macaques. Nat. Med. 10:290293.
38. Hensley, L. E.,, L. E. Fritz,, P. B. Jahrling,, C. L. Karp,, J. W. Huggins, and, T. W. Geisbert. 2004. Interferon-beta 1a and SARS coronavirus replication. Emerg. Infect. Dis. 10:317319.
39. Hogan, R. J.,, G. Gao,, T. Rowe,, P. Bell,, D. Flieder,, J. Paragas,, G. P. Kobinger,, N. A. Wivel,, R. G. Crystal,, J. Boyer,, H. Feldmann,, T. G. Voss, and, J. M. Wilson. 2004. Resolution of primary severe acute respiratory syndrome-associated coronavirus infection requires Stat1. J. Virol. 78:1141611421.
40. Ireland, D. D.,, S. A. Stohlman,, D. R. Hinton,, R. Atkinson, and, C. C. Bergmann. 2008. Type I interferons are essential in controlling neurotropic coronavirus infection irrespective of functional CD8 T cells. J. Virol. 82:300310.
41. Isaacs, A., and, J. Lindenmann. 1957. Virus interference. I. The interferon. Proc. R. Soc. Lond. B Biol. Sci. 147:258267.
42. Ito, T.,, Y. H. Wang, and, Y. J. Liu. 2005. Plasmacytoid dendritic cell precursors/type I interferon-producing cells sense viral infection by Toll-like receptor (TLR) 7 and TLR9. Springer Semin. Immunopathol. 26:221229.
43. Kamitani, W.,, K. Narayanan,, C. Huang,, K. Lokugamage,, T. Ikegami,, N. Ito,, H. Kubo, and, S. Makino. 2006. Severe acute respiratory syndrome coronavirus nsp1 protein suppresses host gene expression by promoting host mRNA degradation. Proc. Natl. Acad. Sci. USA 103:1288512890.
44. Kato, H.,, S. Sato,, M. Yoneyama,, M. Yamamoto,, S. Uematsu,, K. Matsui,, T. Tsujimura,, K. Takeda,, T. Fujita,, O. Takeuchi, and, S. Akira. 2005. Cell type-specific involvement of RIG-I in antiviral response. Immunity 23:1928.
45. Klumperman, J.,, J. K. Locker,, A. Meijer,, M. C. Horzinek,, H. J. Geuze, and, P. J. Rottier. 1994. Coronavirus M proteins accumulate in the Golgi complex beyond the site of virion budding. J. Virol. 68:65236534.
46. Kopecky-Bromberg, S. A.,, L. Martinez-Sobrido,, M. Frieman,, R. A. Baric, and, P. Palese. 2007. Severe acute respiratory syndrome coronavirus open reading frame (ORF) 3b, ORF 6, and nucleocapsid proteins function as interferon antagonists. J. Virol. 81:548557.
47. Krijnse-Locker, J.,, M. Ericsson,, P. J. Rottier, and, G. Griffiths. 1994. Characterization of the budding compartment of mouse hepatitis virus: evidence that transport from the RER to the Golgi complex requires only one vesicular transport step. J. Cell Biol. 124:5570.
48. Ksiazek, T. G.,, D. Erdman,, C. S. Goldsmith,, S. R. Zaki,, T. Peret,, S. Emery,, S. Tong,, C. Urbani,, J. A. Comer,, W. Lim,, P. E. Rollin,, S. F. Dowell,, A. E. Ling,, C. D. Humphrey,, W. J. Shieh,, J. Guarner,, C. D. Paddock,, P. Rota,, B. Fields,, J. DeRisi,, J. Y. Yang,, N. Cox,, J. M. Hughes,, J. W. LeDuc,, W. J. Bellini, and, L. J. Anderson. 2003. A novel coronavirus associated with severe acute respiratory syndrome. N. Engl. J. Med. 348:19531966.
49. Lai, M. M., and, D. Cavanagh. 1997. The molecular biology of coronaviruses. Adv. Virus Res. 48:1100.
50. Laiosa, C. V.,, M. Stadtfeld, and, T. Graf. 2006. Determinants of lymphoid-myeloid lineage diversification. Annu. Rev. Immunol. 24:705738.
51. Lau, S. K.,, P. C. Woo,, K. S. Li,, Y. Huang,, H. W. Tsoi,, B. H. Wong,, S. S. Wong,, S. Y. Leung,, K. H. Chan, and, K. Y. Yuen. 2005. Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats. Proc. Natl. Acad. Sci. USA 102:1404014045.
52. Lau, Y. L., and, J. S. Peiris. 2005. Pathogenesis of severe acute respiratory syndrome. Curr. Opin. Immunol. 17:404410.
53. Laude, H.,, J. Gelfi,, L. Lavenant, and, B. Charley. 1992. Single amino acid changes in the viral glycoprotein M affect induction of alpha interferon by the coronavirus transmissible gastroenteritis virus. J. Virol. 66:743749.
54. Law, H. K.,, C. Y. Cheung,, H. Y. Ng,, S. F. Sia,, Y. O. Chan,, W. Luk,, J. M. Nicholls,, J. S. Peiris, and, Y. L. Lau. 2005. Chemokine up-regulation in SARS-coronavirus-infected, monocyte-derived human dendritic cells. Blood 106:23662374.
55. Lee, S. M.,, S. K. Schommer, and, S. B. Kleiboeker. 2004. Porcine reproductive and respiratory syndrome virus field isolates differ in in vitro interferon phenotypes. Vet. Immunol. Immunopathol. 102:217231.
56. Le May, N.,, S. Dubaele,, L. Proietti De Santis,, A. Billecocq,, M. Bouloy, and, J. M. Egly. 2004. TFIIH transcription factor, a target for the Rift Valley hemorrhagic fever virus. Cell 116:541550.
57. Li, W.,, M. J. Moore,, N. Vasilieva,, J. Sui,, S. K. Wong,, M. A. Berne,, M. Somasundaran,, J. L. Sullivan,, K. Luzuriaga,, T. C. Greenough,, H. Choe, and, M. Farzan. 2003. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426:450454.
58. Li, W.,, Z. Shi,, M. Yu,, W. Ren,, C. Smith,, J. H. Epstein,, H. Wang,, G. Crameri,, Z. Hu,, H. Zhang,, J. Zhang,, J. McEachern,, H. Field,, P. Daszak,, B. T. Eaton,, S. Zhang, and, L. F. Wang. 2005. Bats are natural reservoirs of SARS-like coronaviruses. Science 310:676679.
59. McCray, P. B., Jr.,, L. Pewe,, C. Wohlford-Lenane,, M. Hickey,, L. Manzel,, L. Shi,, J. Netland,, H. P. Jia,, C. Halabi,, C. D. Sigmund,, D. K. Meyerholz,, P. Kirby,, D. C. Look, and, S. Perlman. 2007. Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus. J. Virol. 81:813821.
60. Miller, L. C.,, W. W. Laegreid,, J. L. Bono,, C. G. ChitkoMcKown, and, J. M. Fox. 2004. Interferon type I response in porcine reproductive and respiratory syndrome virus-infected MARC-145 cells. Arch. Virol. 149:24532463.
61. Murray, R. S.,, B. Brown,, D. Brian, and, G. F. Cabirac. 1992. Detection of coronavirus RNA and antigen in multiple sclerosis brain. Ann. Neurol. 31:525533.
62. Narayanan, K.,, A. Maeda,, J. Maeda, and, S. Makino. 2000. Characterization of the coronavirus M protein and nucleocapsid interaction in infected cells. J. Virol. 74:81278134.
63. Narayanan, K.,, C. Huang,, K. Lokugamage,, W. Kamitani,, T. Ikegami,, C. T. Tseng, and, S. Makino. 2008 Severe acute respiratory syndrome coronavirus nsp1 suppresses host gene expression, including that of type I interferon, in infected cells. J. Virol. 82:44714479.
64. Nicholls, J. M.,, L. L. Poon,, K. C. Lee,, W. F. Ng,, S. T. Lai,, C. Y. Leung,, C. M. Chu,, P. K. Hui,, K. L. Mak,, W. Lim,, K. W. Yan,, K. H. Chan,, N. C. Tsang,, Y. Guan,, K. Y. Yuen, and, J. S. Peiris. 2003. Lung pathology of fatal severe acute respiratory syndrome. Lancet 361:17731778.
65. Oostra, M.,, C. A. de Haan,, R. J. de Groot, and, P. J. Rottier. 2006. Glycosylation of the severe acute respiratory syndrome coronavirus triple-spanning membrane proteins 3a and M. J. Virol. 80:23262336.
66. Opstelten, D. J.,, M. C. Horzinek, and, P. J. Rottier. 1993. Complex formation between the spike protein and the membrane protein during mouse hepatitis virus assembly. Adv. Exp. Med. Biol. 342:189195.
67. Opstelten, D. J.,, M. J. Raamsman,, K. Wolfs,, M. C. Horzinek, and, P. J. Rottier. 1995. Envelope glycoprotein interactions in coronavirus assembly. J. Cell Biol. 131:339349.
68. Pedersen, K. W.,, Y. van der Meer,, N. Roos, and, E. J. Snijder. 1999. Open reading frame 1a-encoded subunits of the arterivirus replicase induce endoplasmic reticulum-derived double-membrane vesicles which carry the viral replication complex. J. Virol. 73:20162026.
69. Pei, J.,, M. J. Sekellick,, P. I. Marcus,, I. S. Choi, and, E. W. Collisson. 2001. Chicken interferon type I inhibits infectious bronchitis virus replication and associated respiratory illness. J. Interferon Cytokine Res. 21:10711077.
70. Plagemann, P. G., and, V. Moennig. 1992. Lactate dehydrogenase-elevating virus, equine arteritis virus, and simian hemorrhagic fever virus: a new group of positive-strand RNA viruses. Adv. Virus Res. 41:99192.
71. Reghunathan, R.,, M. Jayapal,, L. Y. Hsu,, H. H. Chng,, D. Tai,, B. P. Leung, and, A. J. Melendez. 2005. Expression profile of immune response genes in patients with severe acute respiratory syndrome. BMC Immunol. 6:2.
72. Rempel, J. D.,, S. J. Murray,, J. Meisner, and, M. J. Buchmeier. 2004. Differential regulation of innate and adaptive immune responses in viral encephalitis. Virology 318:381392.
73. Riffault, S.,, C. Carrat,, L. Besnardeau,, C. La Bonnardiere, and, B. Charley. 1997. In vivo induction of interferon-alpha in pig by non-infectious coronavirus: tissue localization and in situ phenotypic characterization of interferon-alpha-producing cells. J. Gen. Virol. 78 (Pt. 10):24832487.
74. Roth-Cross, J. K.,, L. Martinez-Sobrido,, E. P. Scott,, A. Garcia-Sastre, and, S. R. Weiss. 2007. Inhibition of the alpha/beta interferon response by mouse hepatitis virus at multiple levels. J. Virol. 81:71897199.
75. Samuel, C. E. 2001. Antiviral actions of interferons. Clin. Microbiol. Rev. 14:778809, table of contents.
76. Siegal, F. P.,, N. Kadowaki,, M. Shodell,, P. A. Fitzgerald-Bocarsly,, K. Shah,, S. Ho,, S. Antonenko, and, Y. J. Liu. 1999. The nature of the principal type 1 interferon-producing cells in human blood. Science 284:18351837.
77. Smiley, J. R. 2004. Herpes simplex virus virion host shutoff protein: immune evasion mediated by a viral RNase? J. Virol. 78:10631068.
78. Snijder, E. J., and, J. J. Meulenberg. 1998. The molecular biology of arteriviruses. J. Gen. Virol. 79 (Pt. 5):961979.
79. Snijder, E. J.,, Y. van der Meer,, J. Zevenhoven-Dobbe,, J. J. Onderwater,, J. van der Meulen,, H. K. Koerten, and, A. M. Mommaas. 2006. Ultrastructure and origin of membrane vesicles associated with the severe acute respiratory syndrome coronavirus replication complex. J. Virol. 80:59275940.
80. Spiegel, M.,, A. Pichlmair,, L. Martinez-Sobrido,, J. Cros,, A. Garcia-Sastre,, O. Haller, and, F. Weber. 2005. Inhibition of beta interferon induction by severe acute respiratory syndrome coronavirus suggests a two-step model for activation of interferon regulatory factor 3. J. Virol. 79:20792086.
81. Spiegel, M.,, A. Pichlmair,, E. Muhlberger,, O. Haller, and, F. Weber. 2004. The antiviral effect of interferon-beta against SARS-coronavirus is not mediated by MxA protein. J. Clin. Virol. 30:211213.
82. Spiegel, M.,, K. Schneider,, F. Weber,, M. Weidmann, and, F. T. Hufert. 2006. Interaction of severe acute respiratory syndrome-associated coronavirus with dendritic cells. J. Gen. Virol. 87:19531960.
83. Spiegel, M., and, F. Weber. 2006. Inhibition of cytokine gene expression and induction of chemokine genes in non-lymphatic cells infected with SARS coronavirus. Virol. J. 3:17.
84. Stark, G. R.,, I. M. Kerr,, B. R. Williams,, R. H. Silverman, and, R. D. Schreiber. 1998. How cells respond to interferons. Annu. Rev. Biochem. 67:227264.
85. Stroher, U.,, A. DiCaro,, Y. Li,, J. E. Strong,, F. Aoki,, F. Plummer,, S. M. Jones, and, H. Feldmann. 2004. Severe acute respiratory syndrome-related coronavirus is inhibited by interferon-alpha. J. Infect. Dis. 189:11641167.
86. Taguchi, F., and, S. G. Siddell. 1985. Difference in sensitivity to interferon among mouse hepatitis viruses with high and low virulence for mice. Virology 147:4148.
87. Takeuchi, O., and, S. Akira. 2007. Signaling pathways activated by microorganisms. Curr. Opin. Cell Biol. 19:185191.
88. Thompson, A. J., and, S. A. Locarnini. 2007. Toll-like receptors, RIG-I-like RNA helicases and the antiviral innate immune response. Immunol. Cell Biol. 85:435445.
89. Tooze, J.,, S. Tooze, and, G. Warren. 1984. Replication of coronavirus MHV-A59 in sac- cells: determination of the first site of budding of progeny virions. Eur. J. Cell Biol. 33:281293.
90. Traven, M.,, K. Naslund,, N. Linde,, B. Linde,, A. Silvan,, C. Fossum,, K. O. Hedlund, and, B. Larsson. 2001. Experimental reproduction of winter dysentery in lactating cows using BCV—comparison with BCV infection in milk-fed calves. Vet. Microbiol. 81:127151.
91. Tseng, C. T.,, C. Huang,, P. Newman,, N. Wang,, K. Narayanan,, D. M. Watts,, S. Makino,, M. M. Packard,, S. R. Zaki,, T. S. Chan, and, C. J. Peters. 2007. Severe acute respiratory syndrome coronavirus infection of mice transgenic for the human angiotensin-converting enzyme 2 virus receptor. J. Virol. 81:11621173.
92. Tseng, C. T.,, L. A. Perrone,, H. Zhu,, S. Makino, and, C. J. Peters. 2005. Severe acute respiratory syndrome and the innate immune responses: modulation of effector cell function without productive infection. J. Immunol. 174:79777985.
93. Tseng, C. T.,, J. Tseng,, L. Perrone,, M. Worthy,, V. Popov, and, C. J. Peters. 2005. Apical entry and release of severe acute respiratory syndrome-associated coronavirus in polarized Calu-3 lung epithelial cells. J. Virol. 79:94709479.
94. Uze, G., and, D. Monneron. 2007. IL-28 and IL-29: newcomers to the interferon family. Biochimie 89:729734.
95. Vennema, H.,, G. J. Godeke,, J. W. Rossen,, W. F. Voorhout,, M. C. Horzinek,, D. J. Opstelten, and, P. J. Rottier. 1996. Nucleocapsid-independent assembly of coronavirus-like particles by co-expression of viral envelope protein genes. EMBO J. 15:20202028.
96. Versteeg, G. A.,, P. J. Bredenbeek,, S. H. van den Worm, and, W. J. Spaan. 2007. Group 2 coronaviruses prevent immediate early interferon induction by protection of viral RNA from host cell recognition. Virology 361:1826.
97. Versteeg, G. A.,, O. Slobodskaya, and, W. J. Spaan. 2006. Transcriptional profiling of acute cytopathic murine hepatitis virus infection in fibroblast-like cells. J. Gen. Virol. 87:19611975.
98. Wang, X.,, A. J. Rosa,, H. N. Oliverira,, G. J. Rosa,, X. Guo,, M. Travnicek, and, T. Girshick. 2006. Transcriptome of local innate and adaptive immunity during early phase of infectious bronchitis viral infection. Viral Immunol. 19:768774.
99. Wathelet, M. G.,, M. Orr,, M. B. Frieman, and, R. S. Baric. 2007. Severe acute respiratory syndrome coronavirus evades antiviral signaling: role of nsp1 and rational design of an attenuated strain. J. Virol. 81:1162011633.
100. Weber, F.,, V. Wagner,, S. B. Rasmussen,, R. Hartmann, and, S. R. Paludan. 2006. Double-stranded RNA is produced by positive-strand RNA viruses and DNA viruses but not in detectable amounts by negative-strand RNA viruses. J. Virol. 80:50595064.
101. Wege, H.,, S. Siddell, and, V. ter Meulen. 1982. The biology and pathogenesis of coronaviruses. Curr. Top. Microbiol. Immunol. 99:165200.
102. Weidman, M. K.,, R. Sharma,, S. Raychaudhuri,, P. Kundu,, W. Tsai, and, A. Dasgupta. 2003. The interaction of cytoplasmic RNA viruses with the nucleus. Virus Res. 95:7585.
103. Weiss, S. R., and, S. Navas-Martin. 2005. Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus. Microbiol. Mol. Biol. Rev. 69:635664.
104. Wong, C. K.,, C. W. Lam,, A. K. Wu,, W. K. Ip,, N. L. Lee,, I. H. Chan,, L. C. Lit,, D. S. Hui,, M. H. Chan,, S. S. Chung, and, J. J. Sung. 2004. Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome. Clin. Exp. Immunol. 136:95103.
105. Wong, S.,, S. Lau,, P. Woo, and, K. Y. Yuen. 2007. Bats as a continuing source of emerging infections in humans. Rev. Med. Virol. 17:6791.
106. Ye, Y.,, K. Hauns,, J. O. Langland,, B. L. Jacobs, and, B. G. Hogue. 2007. Mouse hepatitis coronavirus A59 nucleocapsid protein is a type I interferon antagonist. J. Virol. 81:25542563.
107. Yilla, M.,, B. H. Harcourt,, C. J. Hickman,, M. McGrew,, A. Tamin,, C. S. Goldsmith,, W. J. Bellini, and, L. J. Anderson. 2005. SARS-coronavirus replication in human peripheral monocytes/macrophages. Virus Res. 107:93101.
108. Yount, B.,, K. M. Curtis,, E. A. Fritz,, L. E. Hensley,, P. B. Jahrling,, E. Prentice,, M. R. Denison,, T. W. Geisbert, and, R. S. Baric. 2003. Reverse genetics with a full-length infectious cDNA of severe acute respiratory syndrome coronavirus. Proc. Natl. Acad. Sci. USA 100:1299513000.
109. Zhou, H., and, S. Perlman. 2007. Mouse hepatitis virus does not induce beta interferon synthesis and does not inhibit its induction by double-stranded RNA. J. Virol. 81:568574.
110. Ziegler, T.,, S. Matikainen,, E. Ronkko,, P. Osterlund,, M. Sillanpaa,, J. Siren,, R. Fagerlund,, M. Immonen,, K. Melen, and, I. Julkunen. 2005. Severe acute respiratory syndrome coronavirus fails to activate cytokine-mediated innate immune responses in cultured human monocyte-derived dendritic cells. J. Virol. 79:1380013805.
111. Zust, R.,, L. Cervantes-Barragan,, T. Kuri,, G. Blakqori,, F. Weber,, B. Ludewig, and, V. Thiel. 2007. Coronavirus non-structural protein 1 is a major pathogenicity factor: implications for the rational design of coronavirus vaccines. PLoS Pathog. 3:e109.

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