請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/57771
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 葉秀慧(Shiou-Hwei Yeh) | |
dc.contributor.author | Chia-Hsin Wu | en |
dc.contributor.author | 吳佳欣 | zh_TW |
dc.date.accessioned | 2021-06-16T07:02:42Z | - |
dc.date.available | 2016-10-09 | |
dc.date.copyright | 2014-10-09 | |
dc.date.issued | 2014 | |
dc.date.submitted | 2014-07-15 | |
dc.identifier.citation | [1] ICTV. (2012). Order: Nidovirales.
[2] S. van Boheemen, M. de Graaf, C. Lauber, T. M. Bestebroer, V. S. Raj, A. M. Zaki, et al., 'Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans,' MBio, vol. 3, 2012. [3] M. M. C. Lai, S. Perlman, and L. J. Anderson, 'Coronaviridae,' in Fields' virology 5th Edition vol. I, P. M. H. David M. Knipe, Ed., ed. Philadelphia, Pa.: Wolters kluwer/Lippincott Williams & Wilkins, 2007, pp. 1306-1335. [4] R. J. de Groot, S. C. Baker, R. S. Baric, C. S. Brown, C. Drosten, L. Enjuanes, et al., 'Middle East respiratory syndrome coronavirus (MERS-CoV): announcement of the Coronavirus Study Group,' J Virol, vol. 87, pp. 7790-2, Jul 2013. [5] N. Lee, D. Hui, A. Wu, P. Chan, P. Cameron, G. M. Joynt, et al., 'A major outbreak of severe acute respiratory syndrome in Hong Kong,' N Engl J Med, vol. 348, pp. 1986-94, May 15 2003. [6] K. W. Tsang, P. L. Ho, G. C. Ooi, W. K. Yee, T. Wang, M. Chan-Yeung, et al., 'A cluster of cases of severe acute respiratory syndrome in Hong Kong,' N Engl J Med, vol. 348, pp. 1977-85, May 15 2003. [7] H. Pearson, T. Clarke, A. Abbott, J. Knight, and D. Cyranoski, 'SARS: what have we learned?,' Nature, vol. 424, pp. 121-6, Jul 10 2003. [8] T. G. Ksiazek, D. Erdman, C. S. Goldsmith, S. R. Zaki, T. Peret, S. Emery, et al., 'A novel coronavirus associated with severe acute respiratory syndrome,' N Engl J Med, vol. 348, pp. 1953-66, May 15 2003. [9] C. Drosten, S. Gunther, W. Preiser, S. van der Werf, H. R. Brodt, S. Becker, et al., 'Identification of a novel coronavirus in patients with severe acute respiratory syndrome,' N Engl J Med, vol. 348, pp. 1967-76, May 15 2003. [10] S. H. Yeh, H. Y. Wang, C. Y. Tsai, C. L. Kao, J. Y. Yang, H. W. Liu, et al., 'Characterization of severe acute respiratory syndrome coronavirus genomes in Taiwan: molecular epidemiology and genome evolution,' Proc Natl Acad Sci U S A, vol. 101, pp. 2542-7, Feb 24 2004. [11] C. M. Jonassen, T. Kofstad, I. L. Larsen, A. Lovland, K. Handeland, A. Follestad, et al., 'Molecular identification and characterization of novel coronaviruses infecting graylag geese (Anser anser), feral pigeons (Columbia livia) and mallards (Anas platyrhynchos),' J Gen Virol, vol. 86, pp. 1597-607, Jun 2005. [12] L. L. Poon, D. K. Chu, K. H. Chan, O. K. Wong, T. M. Ellis, Y. H. Leung, et al., 'Identification of a novel coronavirus in bats,' J Virol, vol. 79, pp. 2001-9, Feb 2005. [13] P. C. Woo, S. K. Lau, C. M. Chu, K. H. Chan, H. W. Tsoi, Y. Huang, et al., 'Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia,' J Virol, vol. 79, pp. 884-95, Jan 2005. [14] D. K. Chu, L. L. Poon, K. H. Chan, H. Chen, Y. Guan, K. Y. Yuen, et al., 'Coronaviruses in bent-winged bats (Miniopterus spp.),' J Gen Virol, vol. 87, pp. 2461-6, Sep 2006. [15] X. C. Tang, J. X. Zhang, S. Y. Zhang, P. Wang, X. H. Fan, L. F. Li, et al., 'Prevalence and genetic diversity of coronaviruses in bats from China,' J Virol, vol. 80, pp. 7481-90, Aug 2006. [16] M. N. Al-Ahdal, A. A. Al-Qahtani, and S. Rubino, 'Coronavirus respiratory illness in Saudi Arabia,' J Infect Dev Ctries, vol. 6, pp. 692-4, Oct 2012. [17] A. M. Zaki, S. van Boheemen, T. M. Bestebroer, A. D. Osterhaus, and R. A. Fouchier, 'Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia,' N Engl J Med, vol. 367, pp. 1814-20, Nov 8 2012. [18] L. van der Hoek, K. Pyrc, M. F. Jebbink, W. Vermeulen-Oost, R. J. Berkhout, K. C. Wolthers, et al., 'Identification of a new human coronavirus,' Nat Med, vol. 10, pp. 368-73, Apr 2004. [19] R. A. Fouchier, N. G. Hartwig, T. M. Bestebroer, B. Niemeyer, J. C. de Jong, J. H. Simon, et al., 'A previously undescribed coronavirus associated with respiratory disease in humans,' Proc Natl Acad Sci U S A, vol. 101, pp. 6212-6, Apr 20 2004. [20] W. H. O. (WHO). (2013, September). Coronavirus infections. Available: http://www.who.int/csr/disease/coronavirus_infections/en/ [21] P. J. Bredenbeek, C. J. Pachuk, A. F. Noten, J. Charite, W. Luytjes, S. R. Weiss, et al., '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, vol. 18, pp. 1825-32, Apr 11 1990. [22] A. O. Pasternak, W. J. Spaan, and E. J. Snijder, 'Nidovirus transcription: how to make sense...?,' J Gen Virol, vol. 87, pp. 1403-21, Jun 2006. [23] S. G. Sawicki, D. L. Sawicki, and S. G. Siddell, 'A contemporary view of coronavirus transcription,' J Virol, vol. 81, pp. 20-9, Jan 2007. [24] R. K. Williams, G. S. Jiang, and K. V. Holmes, 'Receptor for mouse hepatitis virus is a member of the carcinoembryonic antigen family of glycoproteins,' Proc Natl Acad Sci U S A, vol. 88, pp. 5533-6, Jul 1 1991. [25] G. S. Dveksler, M. N. Pensiero, C. B. Cardellichio, R. K. Williams, G. S. Jiang, K. V. Holmes, et al., 'Cloning of the mouse hepatitis virus (MHV) receptor: expression in human and hamster cell lines confers susceptibility to MHV,' J Virol, vol. 65, pp. 6881-91, Dec 1991. [26] W. Li, M. J. Moore, N. Vasilieva, J. Sui, S. K. Wong, M. A. Berne, et al., 'Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus,' Nature, vol. 426, pp. 450-4, Nov 27 2003. [27] J. Ziebuhr, 'The coronavirus replicase,' Curr Top Microbiol Immunol, vol. 287, pp. 57-94, 2005. [28] E. J. Snijder, P. J. Bredenbeek, J. C. Dobbe, V. Thiel, J. Ziebuhr, L. L. Poon, et al., 'Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage,' J Mol Biol, vol. 331, pp. 991-1004, Aug 29 2003. [29] M. J. van Hemert, A. H. de Wilde, A. E. Gorbalenya, and E. J. Snijder, 'The in vitro RNA synthesizing activity of the isolated arterivirus replication/transcription complex is dependent on a host factor,' J Biol Chem, vol. 283, pp. 16525-36, Jun 13 2008. [30] K. Knoops, M. Kikkert, S. H. Worm, J. C. Zevenhoven-Dobbe, Y. van der Meer, A. J. Koster, et al., 'SARS-coronavirus replication is supported by a reticulovesicular network of modified endoplasmic reticulum,' PLoS Biol, vol. 6, p. e226, Sep 16 2008. [31] S. Hussain, J. Pan, Y. Chen, Y. Yang, J. Xu, Y. Peng, et al., 'Identification of novel subgenomic RNAs and noncanonical transcription initiation signals of severe acute respiratory syndrome coronavirus,' J Virol, vol. 79, pp. 5288-95, May 2005. [32] S. Zuniga, I. Sola, S. Alonso, and L. Enjuanes, 'Sequence motifs involved in the regulation of discontinuous coronavirus subgenomic RNA synthesis,' J Virol, vol. 78, pp. 980-94, Jan 2004. [33] J. L. Moreno, S. Zuniga, L. Enjuanes, and I. Sola, 'Identification of a coronavirus transcription enhancer,' J Virol, vol. 82, pp. 3882-93, Apr 2008. [34] P. A. Mateos-Gomez, S. Zuniga, L. Palacio, L. Enjuanes, and I. Sola, 'Gene N proximal and distal RNA motifs regulate coronavirus nucleocapsid mRNA transcription,' J Virol, vol. 85, pp. 8968-80, Sep 2011. [35] P. A. Mateos-Gomez, L. Morales, S. Zuniga, L. Enjuanes, and I. Sola, 'Long-distance RNA-RNA interactions in the coronavirus genome form high-order structures promoting discontinuous RNA synthesis during transcription,' J Virol, vol. 87, pp. 177-86, Jan 2013. [36] L. Enjuanes, F. Almazan, I. Sola, and S. Zuniga, 'Biochemical aspects of coronavirus replication and virus-host interaction,' Annu Rev Microbiol, vol. 60, pp. 211-30, 2006. [37] S. Fang, B. Chen, F. P. Tay, B. S. Ng, and D. X. Liu, 'An arginine-to-proline mutation in a domain with undefined functions within the helicase protein (Nsp13) is lethal to the coronavirus infectious bronchitis virus in cultured cells,' Virology, vol. 358, pp. 136-47, Feb 5 2007. [38] N. E. Grossoehme, L. Li, S. C. Keane, P. Liu, C. E. Dann, 3rd, J. L. Leibowitz, et al., 'Coronavirus N protein N-terminal domain (NTD) specifically binds the transcriptional regulatory sequence (TRS) and melts TRS-cTRS RNA duplexes,' J Mol Biol, vol. 394, pp. 544-57, Dec 4 2009. [39] S. C. Keane, P. Liu, J. L. Leibowitz, and D. P. Giedroc, 'Functional transcriptional regulatory sequence (TRS) RNA binding and helix destabilizing determinants of murine hepatitis virus (MHV) nucleocapsid (N) protein,' J Biol Chem, vol. 287, pp. 7063-73, Mar 2 2012. [40] S. Zuniga, J. L. Cruz, I. Sola, P. A. Mateos-Gomez, L. Palacio, and L. Enjuanes, 'Coronavirus nucleocapsid protein facilitates template switching and is required for efficient transcription,' J Virol, vol. 84, pp. 2169-75, Feb 2010. [41] K. S. Choi, P. Huang, and M. M. Lai, 'Polypyrimidine-tract-binding protein affects transcription but not translation of mouse hepatitis virus RNA,' Virology, vol. 303, pp. 58-68, Nov 10 2002. [42] H. P. Li, P. Huang, S. Park, and M. M. Lai, 'Polypyrimidine tract-binding protein binds to the leader RNA of mouse hepatitis virus and serves as a regulator of viral transcription,' J Virol, vol. 73, pp. 772-7, Jan 1999. [43] P. Huang and M. M. Lai, 'Heterogeneous nuclear ribonucleoprotein a1 binds to the 3'-untranslated region and mediates potential 5'-3'-end cross talks of mouse hepatitis virus RNA,' J Virol, vol. 75, pp. 5009-17, Jun 2001. [44] K. S. Choi, A. Mizutani, and M. M. Lai, 'SYNCRIP, a member of the heterogeneous nuclear ribonucleoprotein family, is involved in mouse hepatitis virus RNA synthesis,' J Virol, vol. 78, pp. 13153-62, Dec 2004. [45] C. Galan, I. Sola, A. Nogales, B. Thomas, A. Akoulitchev, L. Enjuanes, et al., 'Host cell proteins interacting with the 3' end of TGEV coronavirus genome influence virus replication,' Virology, vol. 391, pp. 304-14, Sep 1 2009. [46] I. Sola, P. A. Mateos-Gomez, F. Almazan, S. Zuniga, and L. Enjuanes, 'RNA-RNA and RNA-protein interactions in coronavirus replication and transcription,' RNA Biol, vol. 8, pp. 237-48, Mar-Apr 2011. [47] L. Xu, S. Khadijah, S. Fang, L. Wang, F. P. Tay, and D. X. Liu, 'The cellular RNA helicase DDX1 interacts with coronavirus nonstructural protein 14 and enhances viral replication,' J Virol, vol. 84, pp. 8571-83, Sep 2010. [48] J. Y. Chen, W. N. Chen, K. M. Poon, B. J. Zheng, X. Lin, Y. X. Wang, et al., 'Interaction between SARS-CoV helicase and a multifunctional cellular protein (Ddx5) revealed by yeast and mammalian cell two-hybrid systems,' Arch Virol, vol. 154, pp. 507-12, 2009. [49] M. M. Parker and P. S. Masters, 'Sequence comparison of the N genes of five strains of the coronavirus mouse hepatitis virus suggests a three domain structure for the nucleocapsid protein,' Virology, vol. 179, pp. 463-8, Nov 1990. [50] K. A. Spencer and J. A. Hiscox, 'Characterisation of the RNA binding properties of the coronavirus infectious bronchitis virus nucleocapsid protein amino-terminal region,' FEBS Lett, vol. 580, pp. 5993-8, Oct 30 2006. [51] S. Zuniga, I. Sola, J. L. Moreno, P. Sabella, J. Plana-Duran, and L. Enjuanes, 'Coronavirus nucleocapsid protein is an RNA chaperone,' Virology, vol. 357, pp. 215-27, Jan 20 2007. [52] K. Narayanan, A. Maeda, J. Maeda, and S. Makino, 'Characterization of the coronavirus M protein and nucleocapsid interaction in infected cells,' J Virol, vol. 74, pp. 8127-34, Sep 2000. [53] K. R. Hurst, L. Kuo, C. A. Koetzner, R. Ye, B. Hsue, and P. S. Masters, 'A major determinant for membrane protein interaction localizes to the carboxy-terminal domain of the mouse coronavirus nucleocapsid protein,' J Virol, vol. 79, pp. 13285-97, Nov 2005. [54] L. Kuo and P. S. Masters, 'Genetic evidence for a structural interaction between the carboxy termini of the membrane and nucleocapsid proteins of mouse hepatitis virus,' J Virol, vol. 76, pp. 4987-99, May 2002. [55] J. A. Hiscox, T. Wurm, L. Wilson, P. Britton, D. Cavanagh, and G. Brooks, 'The coronavirus infectious bronchitis virus nucleoprotein localizes to the nucleolus,' J Virol, vol. 75, pp. 506-12, Jan 2001. [56] R. R. Rowland, R. Kervin, C. Kuckleburg, A. Sperlich, and D. A. Benfield, '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, vol. 64, pp. 1-12, Oct 1999. [57] T. Wurm, H. Chen, T. Hodgson, P. Britton, G. Brooks, and J. A. Hiscox, 'Localization to the nucleolus is a common feature of coronavirus nucleoproteins, and the protein may disrupt host cell division,' J Virol, vol. 75, pp. 9345-56, Oct 2001. [58] D. Yoo, S. K. Wootton, G. Li, C. Song, and R. R. Rowland, 'Colocalization and interaction of the porcine arterivirus nucleocapsid protein with the small nucleolar RNA-associated protein fibrillarin,' J Virol, vol. 77, pp. 12173-83, Nov 2003. [59] M. Surjit, R. Kumar, R. N. Mishra, M. K. Reddy, V. T. Chow, and S. K. Lal, 'The severe acute respiratory syndrome coronavirus nucleocapsid protein is phosphorylated and localizes in the cytoplasm by 14-3-3-mediated translocation,' J Virol, vol. 79, pp. 11476-86, Sep 2005. [60] E. Calvo, D. Escors, J. A. Lopez, J. M. Gonzalez, A. Alvarez, E. Arza, et al., 'Phosphorylation and subcellular localization of transmissible gastroenteritis virus nucleocapsid protein in infected cells,' J Gen Virol, vol. 86, pp. 2255-67, Aug 2005. [61] Y. van der Meer, E. J. Snijder, J. C. Dobbe, S. Schleich, M. R. Denison, W. J. Spaan, et al., 'Localization of mouse hepatitis virus nonstructural proteins and RNA synthesis indicates a role for late endosomes in viral replication,' J Virol, vol. 73, pp. 7641-57, Sep 1999. [62] J. You, B. K. Dove, L. Enjuanes, M. L. DeDiego, E. Alvarez, G. Howell, et al., 'Subcellular localization of the severe acute respiratory syndrome coronavirus nucleocapsid protein,' J Gen Virol, vol. 86, pp. 3303-10, Dec 2005. [63] H. Chen, T. Wurm, P. Britton, G. Brooks, and J. A. Hiscox, 'Interaction of the coronavirus nucleoprotein with nucleolar antigens and the host cell,' J Virol, vol. 76, pp. 5233-50, May 2002. [64] A. G. Bost, R. H. Carnahan, X. T. Lu, and M. R. Denison, 'Four proteins processed from the replicase gene polyprotein of mouse hepatitis virus colocalize in the cell periphery and adjacent to sites of virion assembly,' J Virol, vol. 74, pp. 3379-87, Apr 2000. [65] H. P. Li, X. Zhang, R. Duncan, L. Comai, and M. M. Lai, 'Heterogeneous nuclear ribonucleoprotein A1 binds to the transcription-regulatory region of mouse hepatitis virus RNA,' Proc Natl Acad Sci U S A, vol. 94, pp. 9544-9, Sep 2 1997. [66] X. Zhang, H. P. Li, W. Xue, and M. M. Lai, 'Formation of a ribonucleoprotein complex of mouse hepatitis virus involving heterogeneous nuclear ribonucleoprotein A1 and transcription-regulatory elements of viral RNA,' Virology, vol. 264, pp. 115-24, Nov 10 1999. [67] H. Luo, Q. Chen, J. Chen, K. Chen, X. Shen, and H. Jiang, 'The nucleocapsid protein of SARS coronavirus has a high binding affinity to the human cellular heterogeneous nuclear ribonucleoprotein A1,' FEBS Lett, vol. 579, pp. 2623-8, May 9 2005. [68] Y. Wang and X. Zhang, 'The nucleocapsid protein of coronavirus mouse hepatitis virus interacts with the cellular heterogeneous nuclear ribonucleoprotein A1 in vitro and in vivo,' Virology, vol. 265, pp. 96-109, Dec 5 1999. [69] B. Schelle, N. Karl, B. Ludewig, S. G. Siddell, and V. Thiel, 'Selective replication of coronavirus genomes that express nucleocapsid protein,' J Virol, vol. 79, pp. 6620-30, Jun 2005. [70] B. Yount, M. R. Denison, S. R. Weiss, and R. S. Baric, 'Systematic assembly of a full-length infectious cDNA of mouse hepatitis virus strain A59,' J Virol, vol. 76, pp. 11065-78, Nov 2002. [71] F. Almazan, C. Galan, and L. Enjuanes, 'The nucleoprotein is required for efficient coronavirus genome replication,' J Virol, vol. 78, pp. 12683-8, Nov 2004. [72] R. Casais, V. Thiel, S. G. Siddell, D. Cavanagh, and P. Britton, 'Reverse genetics system for the avian coronavirus infectious bronchitis virus,' J Virol, vol. 75, pp. 12359-69, Dec 2001. [73] R. He, A. Leeson, A. Andonov, Y. Li, N. Bastien, J. Cao, et al., 'Activation of AP-1 signal transduction pathway by SARS coronavirus nucleocapsid protein,' Biochem Biophys Res Commun, vol. 311, pp. 870-6, Nov 28 2003. [74] M. Surjit, B. Liu, V. T. Chow, and S. K. Lal, '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, vol. 281, pp. 10669-81, Apr 21 2006. [75] M. Surjit, B. Liu, S. Jameel, V. T. Chow, and S. K. Lal, 'The SARS coronavirus nucleocapsid protein induces actin reorganization and apoptosis in COS-1 cells in the absence of growth factors,' Biochem J, vol. 383, pp. 13-8, Oct 1 2004. [76] S. A. Kopecky-Bromberg, L. Martinez-Sobrido, M. Frieman, R. A. Baric, and P. Palese, 'Severe acute respiratory syndrome coronavirus open reading frame (ORF) 3b, ORF 6, and nucleocapsid proteins function as interferon antagonists,' J Virol, vol. 81, pp. 548-57, Jan 2007. [77] M. Spiegel, A. Pichlmair, L. Martinez-Sobrido, J. Cros, A. Garcia-Sastre, O. Haller, et al., '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, vol. 79, pp. 2079-86, Feb 2005. [78] X. Zhao, J. M. Nicholls, and Y. G. Chen, 'Severe acute respiratory syndrome-associated coronavirus nucleocapsid protein interacts with Smad3 and modulates transforming growth factor-beta signaling,' J Biol Chem, vol. 283, pp. 3272-80, Feb 8 2008. [79] X. Zuo, M. R. Mattern, R. Tan, S. Li, J. Hall, D. E. Sterner, et al., 'Expression and purification of SARS coronavirus proteins using SUMO-fusions,' Protein Expr Purif, vol. 42, pp. 100-10, Jul 2005. [80] H. Chen, A. Gill, B. K. Dove, S. R. Emmett, C. F. Kemp, M. A. Ritchie, et al., 'Mass spectroscopic characterization of the coronavirus infectious bronchitis virus nucleoprotein and elucidation of the role of phosphorylation in RNA binding by using surface plasmon resonance,' J Virol, vol. 79, pp. 1164-79, Jan 2005. [81] T. C. White, Z. Yi, and B. G. Hogue, 'Identification of mouse hepatitis coronavirus A59 nucleocapsid protein phosphorylation sites,' Virus Res, vol. 126, pp. 139-48, Jun 2007. [82] C. H. Wu, S. H. Yeh, Y. G. Tsay, Y. H. Shieh, C. L. Kao, Y. S. Chen, et al., 'Glycogen synthase kinase-3 regulates the phosphorylation of severe acute respiratory syndrome coronavirus nucleocapsid protein and viral replication,' J Biol Chem, vol. 284, pp. 5229-39, Feb 20 2009. [83] J. S. Liang Lin, Maomao Suna, Jinxiu Liu, Gongjin Xu, Xumin Zhang, Ningzhi Xu, Rong Wang, Siqi Liu, 'Identification of phosphorylation sites in the nucleocapsid protein (N protein) of SARS-coronavirus,' International Journal of Mass Spectrometry, vol. 268, p. 8, 2007. [84] T. Y. Peng, K. R. Lee, and W. Y. Tarn, 'Phosphorylation of the arginine/serine dipeptide-rich motif of the severe acute respiratory syndrome coronavirus nucleocapsid protein modulates its multimerization, translation inhibitory activity and cellular localization,' FEBS J, vol. 275, pp. 4152-63, Aug 2008. [85] S. Fang, L. Xu, M. Huang, F. Qisheng Li, and D. X. Liu, 'Identification of two ATR-dependent phosphorylation sites on coronavirus nucleocapsid protein with nonessential functions in viral replication and infectivity in cultured cells,' Virology, Jul 9 2013. [86] J. Jayaram, S. Youn, and E. W. Collisson, 'The virion N protein of infectious bronchitis virus is more phosphorylated than the N protein from infected cell lysates,' Virology, vol. 339, pp. 127-35, Aug 15 2005. [87] G. C. Shin, Y. S. Chung, I. S. Kim, H. W. Cho, and C. Kang, 'Antigenic characterization of severe acute respiratory syndrome-coronavirus nucleocapsid protein expressed in insect cells: The effect of phosphorylation on immunoreactivity and specificity,' Virus Res, vol. 127, pp. 71-80, Jul 2007. [88] K. A. Spencer, M. Dee, P. Britton, and J. A. Hiscox, 'Role of phosphorylation clusters in the biology of the coronavirus infectious bronchitis virus nucleocapsid protein,' Virology, vol. 370, pp. 373-81, Jan 20 2008. [89] T. C. White and B. G. Hogue, 'Mouse hepatitis coronavirus nucleocapsid phosphorylation,' Adv Exp Med Biol, vol. 581, pp. 157-60, 2006. [90] L. Lin, J. Shao, M. Sun, J. Liu, G. Xu, X. Zhang, et al., 'Identification of phosphorylation sites in the nucleocapsid protein (N protein) of SARS-coronavirus,' International Journal of Mass Spectrometry, vol. 268, pp. 296-303, 2007. [91] G. W. Nelson, S. A. Stohlman, and S. M. Tahara, 'High affinity interaction between nucleocapsid protein and leader/intergenic sequence of mouse hepatitis virus RNA,' J Gen Virol, vol. 81, pp. 181-8, Jan 2000. [92] M. F. Frana, J. N. Behnke, L. S. Sturman, and K. V. Holmes, 'Proteolytic cleavage of the E2 glycoprotein of murine coronavirus: host-dependent differences in proteolytic cleavage and cell fusion,' J Virol, vol. 56, pp. 912-20, Dec 1985. [93] P. I. Hanson and S. W. Whiteheart, 'AAA+ proteins: have engine, will work,' Nat Rev Mol Cell Biol, vol. 6, pp. 519-29, Jul 2005. [94] N. K. Tanner, O. Cordin, J. Banroques, M. Doere, and P. Linder, 'The Q motif: a newly identified motif in DEAD box helicases may regulate ATP binding and hydrolysis,' Mol Cell, vol. 11, pp. 127-38, Jan 2003. [95] Y. Ye, K. Hauns, J. O. Langland, B. L. Jacobs, and B. G. Hogue, 'Mouse hepatitis coronavirus A59 nucleocapsid protein is a type I interferon antagonist,' J Virol, vol. 81, pp. 2554-63, Mar 2007. [96] B. Zhou, J. Liu, Q. Wang, X. Liu, X. Li, P. Li, et al., 'The nucleocapsid protein of severe acute respiratory syndrome coronavirus inhibits cell cytokinesis and proliferation by interacting with translation elongation factor 1alpha,' J Virol, vol. 82, pp. 6962-71, Jul 2008. [97] Y. Shi, D. H. Yang, J. Xiong, J. Jia, B. Huang, and Y. X. Jin, 'Inhibition of genes expression of SARS coronavirus by synthetic small interfering RNAs,' Cell Res, vol. 15, pp. 193-200, Mar 2005. [98] R. Y. Chang and D. A. Brian, 'cis Requirement for N-specific protein sequence in bovine coronavirus defective interfering RNA replication,' J Virol, vol. 70, pp. 2201-7, Apr 1996. [99] M. L. He, B. J. Zheng, Y. Chen, K. L. Wong, J. D. Huang, M. C. Lin, et al., 'Kinetics and synergistic effects of siRNAs targeting structural and replicase genes of SARS-associated coronavirus,' FEBS Lett, vol. 580, pp. 2414-20, May 1 2006. [100] K. S. Yeung and N. A. Meanwell, 'Recent developments in the virology and antiviral research of severe acute respiratory syndrome coronavirus,' Infect Disord Drug Targets, vol. 7, pp. 29-41, Mar 2007. [101] P. McDonagh, P. A. Sheehy, and J. M. Norris, 'In vitro inhibition of feline coronavirus replication by small interfering RNAs,' Vet Microbiol, vol. 150, pp. 220-9, Jun 2 2011. [102] Y. Lan, K. Zhao, W. He, G. Wang, H. Lu, D. Song, et al., 'Inhibition of porcine hemagglutinating encephalomyelitis virus replication by short hairpin RNAs targeting of the nucleocapsid gene in a porcine kidney cell line,' J Virol Methods, vol. 179, pp. 414-8, Feb 2012. [103] S. A. Stohlman, J. O. Fleming, C. D. Patton, and M. M. Lai, 'Synthesis and subcellular localization of the murine coronavirus nucleocapsid protein,' Virology, vol. 130, pp. 527-32, Oct 30 1983. [104] J. P. Blaydes, B. Vojtesek, G. B. Bloomberg, and T. R. Hupp, 'The development and use of phospho-specific antibodies to study protein phosphorylation,' Methods Mol Biol, vol. 99, pp. 177-89, 2000. [105] A. Kudoh, S. Takahama, T. Sawasaki, H. Ode, M. Yokoyama, A. Okayama, et al., 'The phosphorylation of HIV-1 Gag by atypical protein kinase C facilitates viral infectivity by promoting Vpr incorporation into virions,' Retrovirology, vol. 11, p. 9, 2014. [106] P. Linder, P. F. Lasko, M. Ashburner, P. Leroy, P. J. Nielsen, K. Nishi, et al., 'Birth of the D-E-A-D box,' Nature, vol. 337, pp. 121-2, Jan 12 1989. [107] E. Emmott, D. Munday, E. Bickerton, P. Britton, M. A. Rodgers, A. Whitehouse, et al., 'The cellular interactome of the coronavirus infectious bronchitis virus nucleocapsid protein and functional implications for virus biology,' J Virol, vol. 87, pp. 9486-500, Sep 2013. [108] E. van den Born, A. P. Gultyaev, and E. J. Snijder, 'Secondary structure and function of the 5'-proximal region of the equine arteritis virus RNA genome,' RNA, vol. 10, pp. 424-37, Mar 2004. [109] E. van den Born, C. C. Posthuma, A. P. Gultyaev, and E. J. Snijder, 'Discontinuous subgenomic RNA synthesis in arteriviruses is guided by an RNA hairpin structure located in the genomic leader region,' J Virol, vol. 79, pp. 6312-24, May 2005. [110] H. C. Chen, W. C. Lin, Y. G. Tsay, S. C. Lee, and C. J. Chang, 'An RNA helicase, DDX1, interacting with poly(A) RNA and heterogeneous nuclear ribonucleoprotein K,' J Biol Chem, vol. 277, pp. 40403-9, Oct 25 2002. [111] Y. J. Lin and M. M. Lai, 'Deletion mapping of a mouse hepatitis virus defective interfering RNA reveals the requirement of an internal and discontiguous sequence for replication,' J Virol, vol. 67, pp. 6110-8, Oct 1993. [112] Y. N. Kim and S. Makino, 'Characterization of a murine coronavirus defective interfering RNA internal cis-acting replication signal,' J Virol, vol. 69, pp. 4963-71, Aug 1995. [113] J. F. Repass and S. Makino, '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, vol. 72, pp. 7926-33, Oct 1998. [114] M. Ulasli, M. H. Verheije, C. A. de Haan, and F. Reggiori, 'Qualitative and quantitative ultrastructural analysis of the membrane rearrangements induced by coronavirus,' Cell Microbiol, vol. 12, pp. 844-61, Jun 2010. [115] C. Cartier, P. Sivard, C. Tranchat, D. Decimo, C. Desgranges, and V. Boyer, 'Identification of three major phosphorylation sites within HIV-1 capsid. Role of phosphorylation during the early steps of infection,' J Biol Chem, vol. 274, pp. 19434-40, Jul 2 1999. [116] K. I. Ivanov, P. Puustinen, R. Gabrenaite, H. Vihinen, L. Ronnstrand, L. Valmu, et al., 'Phosphorylation of the potyvirus capsid protein by protein kinase CK2 and its relevance for virus infection,' Plant Cell, vol. 15, pp. 2124-39, Sep 2003. [117] L. M. Law, J. C. Everitt, M. D. Beatch, C. F. Holmes, and T. C. Hobman, 'Phosphorylation of rubella virus capsid regulates its RNA binding activity and virus replication,' J Virol, vol. 77, pp. 1764-71, Feb 2003. [118] L. Li, E. A. Monckton, and R. Godbout, 'A role for DEAD box 1 at DNA double-strand breaks,' Mol Cell Biol, vol. 28, pp. 6413-25, Oct 2008. [119] A. O. Adedeji, B. Marchand, A. J. Te Velthuis, E. J. Snijder, S. Weiss, R. L. Eoff, et al., 'Mechanism of nucleic acid unwinding by SARS-CoV helicase,' PLoS One, vol. 7, p. e36521, 2012. [120] A. Seybert, A. Hegyi, S. G. Siddell, and J. Ziebuhr, 'The human coronavirus 229E superfamily 1 helicase has RNA and DNA duplex-unwinding activities with 5'-to-3' polarity,' RNA, vol. 6, pp. 1056-68, Jul 2000. [121] V. Kumar, Y. S. Jung, and P. H. Liang, 'Anti-SARS coronavirus agents: a patent review (2008 - present),' Expert Opin Ther Pat, vol. 23, pp. 1337-48, Oct 2013. [122] Y. S. Keum and Y. J. Jeong, 'Development of chemical inhibitors of the SARS coronavirus: viral helicase as a potential target,' Biochem Pharmacol, vol. 84, pp. 1351-8, Nov 15 2012. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/57771 | - |
dc.description.abstract | 冠狀病毒為具有套膜的 RNA 病毒,含有一全長約∼30 kb的正股單鏈 RNA 基因 (gRNA),可轉譯出多個參與病毒複製的非結構蛋白。除了全長 RNA 基因外,冠狀病毒的複製過程中,亦會產生數個片段較短、可轉譯出結構蛋白的亞基因 RNA (sgmRNA)。所有的病毒RNA,包括gRNA和sgmRNAs,在5’ / 3’兩端序列皆相同,乃是透過一種在合成負股 RNA 時獨特的不連續轉錄機制而產生的。此一過程是由轉錄調節序列 (TRS) 所控制,TRS的位置則分別座落於前導序列 (稱為 leader TRS) ,和在每一個基因前面(稱為 body TRS)。目前認為 sgmRNAs是在負股 RNA 合成過程,藉由leader TRS和互補股body TRS之間的鹼基配對,造成模板切換而發生。然而,調控冠狀病毒進行不連續轉錄到連續轉錄的分子機制仍然不甚清楚。
病毒生活史中表現量最高的sgmRNA可轉譯出核殼蛋白,核殼蛋白被分類為結構蛋白,可與病毒基因纏繞且螺旋包裹入病毒顆粒內。此外,透過反向遺傳學研究,發現核殼蛋白也可調控病毒 gRNA 的合成,但其機制仍然不清楚。已知核殼蛋白是具磷酸化修飾的高鹼性蛋白,而我們的研究發現,在兩種冠狀病毒:SARS冠狀病毒和JHMV鼠冠狀病毒,核殼蛋白的磷酸化修飾主要發生於絲氨酸-精氨酸高度集中區域的絲氨酸位點上。我們同時確認了 GSK-3 為主要負責此磷酸化修飾的磷酸激酶。利用 GSK-3 抑製劑可有效降低感染後病毒效價和感染所造成的細胞病變效應,暗示核殼蛋白的磷酸化與病毒複製過程相關。 本篇研究中更發現經 GSK-3 介導產生磷酸化修飾的核殼蛋白參與 JHMV 不連續轉錄與連續轉錄過程間的轉換。抑制 GSK-3 介導產生磷酸化修飾的核殼蛋白會使得 gRNA 和較大 sgmRNAs 的表現量減少;但較小的 sgmRNAs 合成不受影響。因此,具磷酸化修飾的核殼蛋白可能參與確保全長gRNA產生以及成功生產的成熟病毒顆粒的過程。我們發現細胞內的 DDX1 會被吸引到具磷酸化修飾核殼蛋白的蛋白聚合體以利於 RNA 連續轉錄過程。我們的研究成果證明,冠狀病毒可藉由 GSK-3 介導產生磷酸化修飾的核殼蛋白來參與不連續轉錄過程的調控。 | zh_TW |
dc.description.abstract | Coronaviruses (CoVs) are enveloped RNA viruses containing a ~30 kb positive-sense single-stranded genomic RNA (gRNA), which encodes non-structural proteins involved in viral replication. In addition to the gRNA, several subgenomic mRNAs (sgmRNAs) are generated during viral replication, which encode mainly the structural proteins. All the viral RNAs, including the gRNA and the sgmRNAs, are co-terminal, through a unique discontinuous transcription mechanism during negative-strand RNA synthesis. This discontinuous process is controlled by a conserved transcription regulating sequence (TRS), which is located after the leader sequence (leader TRS) and in front of each gene (body TRS). It has been suggested that through base pairing between the leader TRS and the complementary body TRS, a template-switching event occurs to generate the discontinuous sgmRNAs. However, the molecular mechanisms controlling the switch from discontinuous to continuous transcription in CoV still remain unknown currently.
The most abundant viral sgmRNA encodes the viral nucleocapsid (N) protein, which is categorized as a structural protein to form a helical ribonucleoprotein required for packaging gRNA into the virion. N protein also has non-structural functions in regulating the synthesis of viral gRNA as revealed by reverse genetic studies, but the underlying mechanism is remained unclear. Regarding to the N protein as a highly basic protein with substantial phosphorylation modifications, our study demonstrated that the major phosphorylation sites in both SARS-CoV and JHMV are the Ser residues clustered within the central serine–arginine (SR)-rich motif. We also identified the GSK-3 to be the kinase responsible for this phosphorylation. Treatment with GSK-3 inhibitor can reduce the viral titer and cytopathic effects, suggesting this phosphorylation in N protein is relevant to the viral replication cycle. In the current study, we further discovered a novel function of this GSK-3 mediated N phosphorylation in supporting the transition from discontinuous to continuous transcription of JHMV. Suppression of this specific phosphorylation diminished the synthesis of gRNA and larger sgmRNAs but not the smaller ones. It thus suggested this N phosphorylation might participate in the discontinuous transcription process, with function to ensure the synthesis of full length gRNA and successful production of mature virions. We found the cellular DDX1 is recruited to the phosphorylated N-containing complex and facilitates template readthrough when encountering TRSs for the synthesis of longer viral RNAs. Our results thus demonstrate a unique strategy for the transition from discontinuous to continuous transcription in CoVs via the novel function of the GSK-3 phosphorylated viral N protein. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T07:02:42Z (GMT). No. of bitstreams: 1 ntu-103-D96445002-1.pdf: 6916100 bytes, checksum: 794a570b859bd972d8994cf8cef201cc (MD5) Previous issue date: 2014 | en |
dc.description.tableofcontents | Ph.D. Dissertation Committee Form I
Preface I 摘要 III Abstract IV Index VI List of Figures IX List of Tables XI Abbreviation List XII Chapter 1 Introduction 1 1.1 Coronavirus Taxonomy 1 1.2 Nature Reservoir and Pathogenesis of Coronavirus 1 1.3 Novel Coronaviruses 2 1.4 Genome Characteristics of Coronavirus 2 1.5 Viral Life Cycle of Coronavirus 3 1.6 Discontinuous Transcription of Coronavirus 5 1.6.1 RNA-RNA interactions 5 1.6.2 RNA-protein interactions 6 1.7 Nucleocapsid Protein in Coronavirus 7 1.7.1 Domains of N protein 7 1.7.2 Localization of N protein 7 1.7.3 Functions of N proteins 8 1.7.4 Post-Translational Modification of N proteins 8 Chapter 2 Hypothesis and Purpose 11 Chapter 3 Materials and Methods 12 3.1 Plasmids construction 12 3.2 Cell culture and stable cell lines establishment 13 3.3 Transfection 13 3.4 DDX1 gene knockdown by lentivirus-shRNA 14 3.5 RNA extraction and northern blot analysis 14 3.6 Sucrose gradient sedimentation analysis 15 3.7 Preparation of cell lysates, nuclear/cytosol extraction, and immunoblotting 16 3.8 Chemicals and antibodies 16 3.9 CIP treatment of N protein 17 3.10 Co-immunoprecipitation 18 3.11 Indirect immunofluorescence analysis 18 3.12 Protein identification by mass spectrometry 19 3.13 Quantification of supernatant viral titer and intracellular viral RNAs by real-time RT-PCR 19 3.14 RNA Chip assay 20 3.15 In vitro kinase assay 21 3.16 Pulse-chase analysis 22 3.17 Cell growth assay 22 3.18 Plaque assay 23 3.19 Flow cytometry analysis 23 Chapter 4 Results 24 4.1 Part I: Identification of the phosphorylated sites and responsible major kinase of SARS-CoV N and JHMV N 24 4.1.1 The N protein of SARS-CoV is phosphorylated in VeroE6 and 293T cells 24 4.1.2 The Ser-177 residue of SARS-CoV N appears to be fully phosphorylated in vivo 24 4.1.3 The phosphorylation sites of SARS-CoV N protein cluster at the central SR-rich region 25 4.1.4 GSK-3 is the putative kinase contributing to SARS-CoV N phosphorylation at the SR-rich region 26 4.1.5 SARS-CoV N can interact with GSK-3 α and GSK-3β in vivo and can be phosphorylated by GSK-3 α and GSK-3β in vitro 27 4.1.6 Identification of the Critical Serine Residues Phosphorylated by GSK-3 on SARS-CoV N Protein 27 4.1.7 GSK-3 inhibitor suppressed the replication of SARS-CoV 30 4.1.8 GSK-3 is also involved in regulating the phosphorylation of JHMV N protein 31 4.2 Part II: Investigation of the functional role of phosphorylated N in JHMV RNA transcription 34 4.2.1 GSK-3 inhibitors reduce viral RNA synthesis 34 4.2.2 GSK-3-mediated N phosphorylation upregulates the synthesis of gRNA and larger sgmRNAs of JHMV 35 4.2.3 Sucrose fractions containing the phosphorylated N protein complex are associated with CoV RNA synthesis at the early stage of viral replication 36 4.2.4 The RNA helicase DDX1 interacts with phosphorylated N in JHMV-infected cells 38 4.2.5 DDX1 is critical for the synthesis of larger JHMV RNAs and gRNA in a helicase enzyme activity-dependent manner 39 4.2.6 Preferential binding of phosphorylated N and the DDX1 complex to the 5’ viral genome to increase the synthesis of larger viral RNAs 41 Chapter 5. Discussion 43 Chapter 6. Conclusion 52 Figures and Tables 53 References 76 Appendices 87 | |
dc.language.iso | en | |
dc.title | 冠狀病毒核殼蛋白磷酸化修飾調控病毒 RNA 轉錄過程之分子機制研究 | zh_TW |
dc.title | The Mechanism for the Phosphorylation of Coronavirus Nucleocapsid Protein in Regulating the Discontinuous RNA Transcription Process | en |
dc.type | Thesis | |
dc.date.schoolyear | 102-2 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 陳培哲(Pei-Jer Chen),陳美如(Mei-Ru Chen),廖經倫(Ching-Len Liao),林宜玲(Yi-Lin Lin) | |
dc.subject.keyword | 冠狀病毒,核殼蛋白,磷酸化修飾,不連續轉錄,嚴重急性呼吸系統綜合症, | zh_TW |
dc.subject.keyword | coronavirus,SARS,nucleocapsid,phosphorylation,discontinuous transcription, | en |
dc.relation.page | 87 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2014-07-15 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 微生物學研究所 | zh_TW |
顯示於系所單位: | 微生物學科所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-103-1.pdf 目前未授權公開取用 | 6.75 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。