Molecular Basis of Coronavirus Virulence and Vaccine Development

Advances in Virus Research

Volumn 96, Issue , 2016, Pages 245-286

  Enjuanes, L ^a   Zuniga S ^a   Castano Rodriguez C ^a   Gutierrez Alvarez, J ^a   Canton, J ^a   Sola, I ^a  

^a CSIC   (Spain)

Author keywords

Biosafety; Human coronaviruses; Immune response; Innate immune response; Live attenuated vaccines; Protection; Vaccines; Virulence

Indexed keywords

INACTIVATED VACCINE; SUBUNIT VACCINE; VIRUS ANTIGEN; VIRUS VACCINE;

ANIMAL; B LYMPHOCYTE; BIOSYNTHESIS; CORONAVIRUS INFECTIONS; DISEASE MODEL; DRUG EFFECTS; GENETICS; HUMAN; IMMUNOLOGY; INNATE IMMUNITY; MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS; PATHOGENICITY; PATHOLOGY; SARS CORONAVIRUS; SEVERE ACUTE RESPIRATORY SYNDROME; T LYMPHOCYTE; VACCINATION; VIROLOGY; VIRULENCE; VIRUS GENOME;

ANIMALS; ANTIGENS, VIRAL; B-LYMPHOCYTES; CORONAVIRUS INFECTIONS; DISEASE MODELS, ANIMAL; GENOME, VIRAL; HUMANS; IMMUNITY, INNATE; MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS; SARS VIRUS; SEVERE ACUTE RESPIRATORY SYNDROME; T-LYMPHOCYTES; VACCINATION; VACCINES, INACTIVATED; VACCINES, SUBUNIT; VIRAL VACCINES; VIRULENCE;

EID: 84994181160     PISSN: 00653527     EISSN: 15578399     Source Type: Book Series    
DOI: 10.1016/bs.aivir.2016.08.003     Document Type: Chapter

References (189)

1. Adedeji, A.O., Sarafianos, S.G., Antiviral drugs specific for coronaviruses in preclinical development. Curr. Opin. Virol. 8 (2014), 45–53.
2. Agrawal, A.S., Garron, T., Tao, X., Peng, B.H., Wakamiya, M., Chan, T.S., et al. Generation of a transgenic mouse model of Middle East respiratory syndrome coronavirus infection and disease. J. Virol. 89 (2015), 3659–3670.
3. Almazan, F., Gonzalez, J.M., Penzes, Z., Izeta, A., Calvo, E., Plana-Duran, J., et al. Engineering the largest RNA virus genome as an infectious bacterial artificial chromosome. Proc. Natl. Acad. Sci. U.S.A. 97 (2000), 5516–5521.
4. Almazan, F., DeDiego, M.L., Sola, I., Zuñiga, S., Nieto-Torres, J.L., Marquez-Jurado, S., et al. Engineering a replication-competent, propagation-defective Middle East respiratory syndrome coronavirus as a vaccine candidate. MBio, 4, 2013 e00650-13.
5. Altenburg, A.F., Kreijtz, J.H., de Vries, R.D., Song, F., Fux, R., Rimmelzwaan, G.F., et al. Modified vaccinia virus ankara (MVA) as production platform for vaccines against influenza and other viral respiratory diseases. Viruses 6 (2014), 2735–2761.
6. An, S., Chen, C.J., Yu, X., Leibowitz, J.L., Makino, S., Induction of apoptosis in murine coronavirus-infected cultured cells and demonstration of E protein as an apoptosis inducer. J. Virol. 73 (1999), 7853–7859.
7. Angelini, M.M., Akhlaghpour, M., Neuman, B.W., Buchmeier, M.J., Severe acute respiratory syndrome coronavirus nonstructural proteins 3, 4, and 6 induce double-membrane vesicles. MBio, 4, 2013 e00524-13.
8. Barnard, D.L., Kumaki, Y., Recent developments in anti-severe acute respiratory syndrome coronavirus chemotherapy. Futur. Virol. 6 (2011), 615–631.
9. Barretto, N., Jukneliene, D., Ratia, K., Chen, Z., Mesecar, A.D., Baker, S.C., The papain-like protease of severe acute respiratory syndrome coronavirus has deubiquitinating activity. J. Virol. 79 (2005), 15189–15198.
10. Bolles, M., Deming, D., Long, K., Agnihothram, S., Whitmore, A., Ferris, M., et al. A double-inactivated severe acute respiratory syndrome coronavirus vaccine provides incomplete protection in mice and induces increased eosinophilic proinflammatory pulmonary response upon challenge. J. Virol. 85 (2011), 12201–12215.
11. Butler, N., Pewe, L., Trandem, K., Perlman, S., Murine encephalitis caused by HCoV-OC43, a human coronavirus with broad species specificity, is partly immune-mediated. Virology 347 (2006), 410–421.
12. Chan, R.W., Chan, M.C., Agnihothram, S., Chan, L.L., Kuok, D.I., Fong, J.H., et al. Tropism of and innate immune responses to the novel human betacoronavirus lineage C virus in human ex vivo respiratory organ cultures. J. Virol. 87 (2013), 6604–6614.
13. Channappanavar, R., Fett, C., Zhao, J., Meyerholz, D.K., Perlman, S., Virus-specific memory CD8 T cells provide substantial protection from lethal severe acute respiratory syndrome coronavirus infection. J. Virol. 88 (2014), 11034–11044.
14. Channappanavar, R., Fehr, A.R., Vijay, R., Mack, M., Zhao, J., Meyerholz, D.K., et al. Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice. Cell Host Microbe 19 (2016), 181–193.
15. Chen, Z., Wang, Y., Ratia, K., Mesecar, A.D., Wilkinson, K.D., Baker, S.C., Proteolytic processing and deubiquitinating activity of papain-like proteases of human coronavirus NL63. J. Virol. 81 (2007), 6007–6018.
16. Chen, J., Lau, Y.F., Lamirande, E.W., Paddock, C.D., Bartlett, J.H., Zaki, S.R., et al. Cellular immune responses to severe acute respiratory syndrome coronavirus (SARS-CoV) infection in senescent BALB/c mice: CD4 + T cells are important in control of SARS-CoV infection. J. Virol. 84 (2010), 1289–1301.
17. Chen, X., Yang, X., Zheng, Y., Yang, Y., Xing, Y., Chen, Z., SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex. Protein Cell 5 (2014), 369–381.
18. Cheung, C.Y., Poon, L.L., Ng, I.H., Luk, W., Sia, S.F., Wu, M.H., et al. Cytokine responses in severe acute respiratory syndrome coronavirus-infected macrophages in vitro: possible relevance to pathogenesis. J. Virol. 79 (2005), 7819–7826.
19. Chu, H., Zhou, J., Wong, B.H., Li, C., Cheng, Z.S., Lin, X., et al. Productive replication of Middle East respiratory syndrome coronavirus in monocyte-derived dendritic cells modulates innate immune response. Virology 454–455 (2014), 197–205.
20. Chu, H., Zhou, J., Wong, B.H., Li, C., Chan, J.F., Cheng, Z.S., et al. Middle East respiratory syndrome coronavirus efficiently infects human primary T lymphocytes and activates the extrinsic and intrinsic apoptosis pathways. J. Infect. Dis. 213 (2016), 904–914.
21. Clementz, M.A., Chen, Z., Banach, B.S., Wang, Y., Sun, L., Ratia, K., et al. Deubiquitinating and interferon antagonism activities of coronavirus papain-like proteases. J. Virol. 84 (2010), 4619–4629.
22. Cockrell, A.S., Peck, K.M., Yount, B.L., Agnihothram, S.S., Scobey, T., Curnes, N.R., et al. Mouse dipeptidyl peptidase 4 is not a functional receptor for Middle East respiratory syndrome coronavirus infection. J. Virol. 88 (2014), 5195–5199.
23. Coleman, C.M., Liu, Y.V., Mu, H., Taylor, J.K., Massare, M., Flyer, D.C., et al. Purified coronavirus spike protein nanoparticles induce coronavirus neutralizing antibodies in mice. Vaccine 32 (2014), 3169–3174.
24. Coleman, C.M., Matthews, K.L., Goicochea, L., Frieman, M.B., Wild-type and innate immune-deficient mice are not susceptible to the Middle East respiratory syndrome coronavirus. J. Gen. Virol. 95 (2014), 408–412.
25. Collins, A.R., In vitro detection of apoptosis in monocytes/macrophages infected with human coronavirus. Clin. Diagn. Lab. Immunol. 9 (2002), 1392–1395.
26. Corman, V.M., Ithete, N.L., Richards, L.R., Schoeman, M.C., Preiser, W., Drosten, C., et al. Rooting the phylogenetic tree of middle East respiratory syndrome coronavirus by characterization of a conspecific virus from an African bat. J. Virol. 88 (2014), 11297–11303.
27. Das, A.T., Zhou, X., Metz, S.W., Vink, M.A., Berkhout, B., Selecting the optimal Tet-On system for doxycycline-inducible gene expression in transiently transfected and stably transduced mammalian cells. Biotechnol. J. 11 (2016), 71–79.
28. Day, C.W., Baric, R., Cai, S.X., Frieman, M., Kumaki, Y., Morrey, J.D., et al. A new mouse-adapted strain of SARS-CoV as a lethal model for evaluating antiviral agents in vitro and in vivo. Virology 395 (2009), 210–222.
29. de Groot, R.J., Baker, S.C., Baric, R., Enjuanes, L., Gorbalenya, A.E., Holmes, K.V., et al. Family coronaviridae. King, A.M.Q., Adams, M.J., Carstens, E.B., Lefkowitz, E.J., (eds.) Virus Taxonomy, 2012, Elsevier, Amsterdam, 774–796.
30. DeDiego, M.L., Alvarez, E., Almazan, F., Rejas, M.T., Lamirande, E., Roberts, A., et al. A severe acute respiratory syndrome coronavirus that lacks the E gene is attenuated in vitro and in vivo. J. Virol. 81 (2007), 1701–1713.
31. DeDiego, M.L., Nieto-Torres, J.L., Jimenez-Guardeño, J.M., Regla-Nava, J.A., Alvarez, E., Oliveros, J.C., et al. Severe acute respiratory syndrome coronavirus envelope protein regulates cell stress response and apoptosis. PLoS Pathog., 7, 2011, e1002315.
32. DeDiego, M.L., Nieto-Torres, J.L., Jimenez-Guardeño, J.M., Regla-Nava, J.A., Castaño-Rodriguez, C., Fernandez-Delgado, R., et al. Coronavirus virulence genes with main focus on SARS-CoV envelope gene. Virus Res. 194 (2014), 124–137.
33. DeDiego, M.L., Nieto-Torres, J.L., Regla-Nava, J.A., Jimenez-Guardeño, J.M., Fernandez-Delgado, R., Fett, C., et al. Inhibition of NF-kappaB mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival. J. Virol. 88 (2014), 913–924.
34. Desforges, M., Desjardins, J., Zhang, C., Talbot, P.J., The acetyl-esterase activity of the hemagglutinin-esterase protein of human coronavirus OC43 strongly enhances the production of infectious virus. J. Virol. 87 (2013), 3097–3107.
35. Dijkman, R., Jebbink, M.F., Wilbrink, B., Pyrc, K., Zaaijer, H.L., Minor, P.D., et al. Human coronavirus 229E encodes a single ORF4 protein between the spike and the envelope genes. Virol. J., 3, 2006, 106.
36. Dijkman, R., Jebbink, M.F., Koekkoek, S.M., Deijs, M., Jonsdottir, H.R., Molenkamp, R., et al. Isolation and characterization of current human coronavirus strains in primary human epithelial cell cultures reveal differences in target cell tropism. J. Virol. 87 (2013), 6081–6090.
37. Donaldson, E.F., Yount, B., Sims, A.C., Burkett, S., Pickles, R.J., Baric, R.S., Systematic assembly of a full-length infectious clone of human coronavirus NL63. J. Virol. 82 (2008), 11948–11957.
38. Drosten, C., Muth, D., Corman, V.M., Hussain, R., Al Masri, M., HajOmar, W., et al. An observational, laboratory-based study of outbreaks of middle East respiratory syndrome coronavirus in Jeddah and Riyadh, kingdom of Saudi Arabia, 2014. Clin. Infect. Dis. 60 (2015), 369–377.
39. Du, L., Jiang, S., Middle East respiratory syndrome: current status and future prospects for vaccine development. Expert. Opin. Biol. Ther. 15 (2015), 1647–1651.
40. Du, L., Zhao, G., Lin, Y., Sui, H., Chan, C., Ma, S., et al. Intranasal vaccination of recombinant adeno-associated virus encoding receptor-binding domain of severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein induces strong mucosal immune responses and provides long-term protection against SARS-CoV infection. J. Immunol. 180 (2008), 948–956.
41. Du, L., Zhao, G., Kou, Z., Ma, C., Sun, S., Poon, V.K., et al. Identification of receptor-binding domain in S protein of the novel human coronavirus MERS-CoV as an essential target for vaccine development. J. Virol. 17 (2013), 9939–9942.
42. Eckerle, L.D., Becker, M.M., Halpin, R.A., Li, K., Venter, E., Lu, X., et al. Infidelity of SARS-CoV nsp14-exonuclease mutant virus replication is revealed by complete genome sequencing. PLoS Pathog., 6, 2010, e1000896.
43. Enjuanes, L., DeDiego, M.L., Alvarez, E., Deming, D., Sheahan, T., Baric, R., Vaccines to prevent severe acute respiratory syndrome coronavirus-induced disease. Virus Res. 133 (2008), 45–62.
44. Eriksson, K.K., Cervantes-Barragan, L., Ludewig, B., Thiel, V., Mouse hepatitis virus liver pathology is dependent on ADP-ribose-1″-phosphatase, a viral function conserved in the alpha-like supergroup. J. Virol. 82 (2008), 12325–12334.
45. Escriou, N., Callendret, B., Lorin, V., Combredet, C., Marianneau, P., Fevrier, M., et al. Protection from SARS coronavirus conferred by live measles vaccine expressing the spike glycoprotein. Virology 452–453 (2014), 32–41.
46. Falzarano, D., de Wit, E., Feldmann, F., Rasmussen, A.L., Okumura, A., Peng, X., et al. Infection with MERS-CoV causes lethal pneumonia in the common marmoset. PLoS Pathog., 10, 2014, e1004250.
47. Favreau, D.J., Desforges, M., St-Jean, J.R., Talbot, P.J., A human coronavirus OC43 variant harboring persistence-associated mutations in the S glycoprotein differentially induces the unfolded protein response in human neurons as compared to wild-type virus. Virology 395 (2009), 255–267.
48. Fett, C., DeDiego, M.L., Regla-Nava, J.A., Enjuanes, L., Perlman, S., Complete protection against severe acute respiratory syndrome coronavirus-mediated lethal respiratory disease in aged mice by immunization with a mouse-adapted virus lacking E protein. J. Virol. 87 (2013), 6551–6559.
49. Frieman, M., Ratia, K., Johnston, R.E., Mesecar, A.D., Baric, R.S., Severe acute respiratory syndrome coronavirus papain-like protease ubiquitin-like domain and catalytic domain regulate antagonism of IRF3 and NF-kappaB signaling. J. Virol. 83 (2009), 6689–6705.
50. Frieman, M., Yount, B., Agnihothram, S., Page, C., Donaldson, E., Roberts, A., et al. Molecular determinants of severe acute respiratory syndrome coronavirus pathogenesis and virulence in young and aged mouse models of human disease. J. Virol. 86 (2012), 884–897.
51. Graham, R.L., Becker, M.M., Eckerle, L.D., Bolles, M., Denison, M.R., Baric, R.S., A live, impaired-fidelity coronavirus vaccine protects in an aged, immunocompromised mouse model of lethal disease. Nat. Med. 18 (2012), 1820–1826.
52. Gretebeck, L.M., Subbarao, K., Animal models for SARS and MERS coronaviruses. Curr. Opin. Virol. 13 (2015), 123–129.
53. Gu, J., Gong, E., Zhang, B., Zheng, J., Gao, Z., Zhong, Y., et al. Multiple organ infection and the pathogenesis of SARS. J. Exp. Med. 202 (2005), 415–424.
54. Guo, X., Deng, Y., Chen, H., Lan, J., Wang, W., Zou, X., et al. Systemic and mucosal immunity in mice elicited by a single immunization with human adenovirus type 5 or 41 vector-based vaccines carrying the spike protein of Middle East respiratory syndrome coronavirus. Immunology 145 (2015), 476–484.
55. Haagmans, B.L., van den Brand, J.M., Provacia, L.B., Raj, V.S., Stittelaar, K.J., Getu, S., et al. Asymptomatic Middle East respiratory syndrome coronavirus infection in rabbits. J. Virol. 89 (2015), 6131–6135.
56. Haagmans, B.L., van den Brand, J.M., Raj, V.S., Volz, A., Wohlsein, P., Smits, S.L., et al. An orthopoxvirus-based vaccine reduces virus excretion after MERS-CoV infection in dromedary camels. Science 351 (2016), 77–81.
57. Hetz, C., The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat. Rev. Mol. Cell Biol. 13 (2012), 89–102.
58. Honda-Okubo, Y., Barnard, D., Ong, C.H., Peng, B.H., Tseng, C.T., Petrovsky, N., Severe acute respiratory syndrome-associated coronavirus vaccines formulated with delta inulin adjuvants provide enhanced protection while ameliorating lung eosinophilic immunopathology. J. Virol. 89 (2015), 2995–3007.
59. Hou, Y.X., Peng, C., Han, Z.G., Zhou, P., Chen, J.G., Shi, Z.L., Immunogenicity of the spike glycoprotein of bat SARS-like coronavirus. Virol. Sin. 25 (2010), 36–44.
60. Huang, X., Dong, W., Milewska, A., Golda, A., Qi, Y., Zhu, Q.K., et al. Human coronavirus HKU1 spike protein uses O-acetylated sialic acid as an attachment receptor determinant and employs hemagglutinin-esterase protein as a receptor-destroying enzyme. J. Virol. 89 (2015), 7202–7213.
61. Iwata-Yoshikawa, N., Uda, A., Suzuki, T., Tsunetsugu-Yokota, Y., Sato, Y., Morikawa, S., et al. Effects of Toll-like receptor stimulation on eosinophilic infiltration in lungs of BALB/c mice immunized with UV-inactivated severe acute respiratory syndrome-related coronavirus vaccine. J. Virol. 88 (2014), 8597–8614.
62. Jacomy, H., Talbot, P.J., Vacuolating encephalitis in mice infected by human coronavirus OC43. Virology 315 (2003), 20–33.
63. Jaume, M., Yip, M.S., Kam, Y.W., Cheung, C.Y., Kien, F., Roberts, A., et al. SARS CoV subunit vaccine: antibody-mediated neutralisation and enhancement. Hong Kong Med. J. 18 (2012), 31–36.
64. Jiang, L., Wang, N., Zuo, T., Shi, X., Poon, K.M., Wu, Y., et al. Potent neutralization of MERS-CoV by human neutralizing monoclonal antibodies to the viral spike glycoprotein. Sci. Transl. Med., 6, 2014, 234ra259.
65. Jimenez-Guardeño, J.M., Nieto-Torres, J.L., DeDiego, M.L., Regla-Nava, J.A., Fernandez-Delgado, R., Castaño-Rodriguez, C., et al. The PDZ-binding motif of severe acute respiratory syndrome coronavirus envelope protein Is a determinant of viral pathogenesis. PLoS Pathog., 10, 2014, e1004320.
66. Jimenez-Guardeno, J.M., Regla-Nava, J.A., Nieto-Torres, J.L., DeDiego, M.L., Castano-Rodriguez, C., Fernandez-Delgado, R., et al. Identification of the mechanisms causing reversion to virulence in an attenuated SARS-CoV for the design of a genetically stable vaccine. PLoS Pathog., 11, 2015, e1005215.
67. Keyaerts, E., Li, S., Vijgen, L., Rysman, E., Verbeeck, J., Van Ranst, M., et al. Antiviral activity of chloroquine against human coronavirus OC43 infection in newborn mice. Antimicrob. Agents Chemother. 53 (2009), 3416–3421.
68. Kilianski, A., Baker, S.C., Cell-based antiviral screening against coronaviruses: developing virus-specific and broad-spectrum inhibitors. Antivir. Res. 101 (2014), 105–112.
69. Kim, E., Okada, K., Kenniston, T., Raj, V.S., AlHajri, M.M., Farag, E.A., et al. Immunogenicity of an adenoviral-based Middle East respiratory syndrome coronavirus vaccine in BALB/c mice. Vaccine 32 (2014), 5975–5982.
70. Kindler, E., Jonsdottir, H.R., Muth, D., Hamming, O.J., Hartmann, R., Rodriguez, R., et al. Efficient replication of the novel human betacoronavirus EMC on primary human epithelium highlights its zoonotic potential. MBio 4 (2013), e00611–e00612.
71. Kirkpatrick, B.D., Whitehead, S.S., Pierce, K.K., Tibery, C.M., Grier, P.L., Hynes, N.A., et al. The live attenuated dengue vaccine TV003 elicits complete protection against dengue in a human challenge model. Sci. Transl. Med. 8 (2016), 330–336.
72. Kuri, T., Eriksson, K.K., Putics, A., Zust, R., Snijder, E.J., Davidson, A.D., et al. The ADP-ribose-1″-monophosphatase domains of severe acute respiratory syndrome coronavirus and human coronavirus 229E mediate resistance to antiviral interferon responses. J. Gen. Virol. 92 (2011), 1899–1905.
73. Lamirande, E.W., DeDiego, M.L., Roberts, A., Jackson, J.P., Alvarez, E., Sheahan, T., et al. A live attenuated SARS coronavirus is immunogenic and efficacious in golden Syrian hamsters. J. Virol. 82 (2008), 7721–7724.
74. Lan, J., Yao, Y., Deng, Y., Chen, H., Lu, G., Wang, W., et al. Recombinant receptor binding domain protein induces partial protective immunity in rhesus macaques against Middle East respiratory syndrome coronavirus challenge. EBioMedicine 2 (2015), 1438–1446.
75. Lassnig, C., Sanchez, C.M., Egerbacher, M., Walter, I., Majer, S., Kolbe, T., et al. Development of a transgenic mouse model susceptible to human coronavirus 229E. Proc. Natl. Acad. Sci. U.S.A. 102 (2005), 8275–8280.
76. Law, H.K., Cheung, C.Y., Ng, H.Y., Sia, S.F., Chan, Y.O., Luk, W., et al. Chemokine up-regulation in SARS-coronavirus-infected, monocyte-derived human dendritic cells. Blood 106 (2005), 2366–2374.
77. Law, H.K., Cheung, C.Y., Sia, S.F., Chan, Y.O., Peiris, J.S., Lau, Y.L., Toll-like receptors, chemokine receptors and death receptor ligands responses in SARS coronavirus infected human monocyte derived dendritic cells. BMC Immunol., 10, 2009, 35.
78. Lee, N., Hui, D., Wu, A., Chan, P., Cameron, P., Joynt, G., et al. A major outbreak of severe acute respiratory syndrome in Hong Kong. N. Engl. J. Med. 348 (2003), 1986–1994.
79. Li, J., Ulitzky, L., Silberstein, E., Taylor, D.R., Viscidi, R., Immunogenicity and protection efficacy of monomeric and trimeric recombinant SARS coronavirus spike protein subunit vaccine candidates. Viral Immunol. 26 (2013), 126–132.
80. Li, K., Wohlford-Lenane, C., Perlman, S., Zhao, J., Jewell, A.K., Reznikov, L.R., et al. Middle East respiratory syndrome coronavirus causes multiple organ damage and lethal disease in mice transgenic for human dipeptidyl peptidase 4. J. Infect. Dis. 213 (2016), 712–722.
81. Liu, Y.V., Massare, M.J., Barnard, D.L., Kort, T., Nathan, M., Wang, L., et al. Chimeric severe acute respiratory syndrome coronavirus (SARS-CoV) S glycoprotein and influenza matrix 1 efficiently form virus-like particles (VLPs) that protect mice against challenge with SARS-CoV. Vaccine 29 (2011), 6606–6613.
82. Lokugamage, K.G., Narayanan, K., Nakagawa, K., Terasaki, K., Ramirez, S.I., Tseng, C.T., et al. Middle East Respiratory Syndrome coronavirus nsp1 inhibits host gene expression by selectively targeting mRNAs transcribed in the nucleus while sparing mRNAs of cytoplasmic origin. J. Virol. 89 (2015), 10970–10981.
83. Ma, C., Li, Y., Wang, L., Zhao, G., Tao, X., Tseng, C.T., et al. Intranasal vaccination with recombinant receptor-binding domain of MERS-CoV spike protein induces much stronger local mucosal immune responses than subcutaneous immunization: implication for designing novel mucosal MERS vaccines. Vaccine 32 (2014), 2100–2108.
84. Ma, C., Wang, L., Tao, X., Zhang, N., Yang, Y., Tseng, C.T., et al. Searching for an ideal vaccine candidate among different MERS coronavirus receptor-binding fragments—the importance of immunofocusing in subunit vaccine design. Vaccine 32 (2014), 6170–6176.
85. Markusic, D., Oude-Elferink, R., Das, A.T., Berkhout, B., Seppen, J., Comparison of single regulated lentiviral vectors with rtTA expression driven by an autoregulatory loop or a constitutive promoter. Nucleic Acids Res., 33, 2005, e63.
86. Matthews, K.L., Coleman, C.M., van der Meer, Y., Snijder, E.J., Frieman, M.B., The ORF4b-encoded accessory proteins of Middle East respiratory syndrome coronavirus and two related bat coronaviruses localize to the nucleus and inhibit innate immune signalling. J. Gen. Virol. 95 (2014), 874–882.
87. Mayer, K., Nellessen, C., Hahn-Ast, C., Schumacher, M., Pietzonka, S., Eis-Hubinger, A.M., et al. Fatal outcome of human coronavirus NL63 infection despite successful viral elimination by IFN-alpha in a patient with newly diagnosed ALL. Eur. J. Haematol. 97 (2016), 208–210.
88. Menachery, V.D., Yount, B.L. Jr., Josset, L., Gralinski, L.E., Scobey, T., Agnihothram, S., et al. Attenuation and restoration of severe acute respiratory syndrome coronavirus mutant lacking 2′-o-methyltransferase activity. Eur. J. Haematol. 88 (2014), 4251–4264.
89. Mesel-Lemoine, M., Millet, J., Vidalain, P.O., Law, H., Vabret, A., Lorin, V., et al. A human coronavirus responsible for the common cold massively kills dendritic cells but not monocytes. J. Virol. 86 (2012), 7577–7587.
90. Mielech, A.M., Kilianski, A., Baez-Santos, Y.M., Mesecar, A.D., Baker, S.C., MERS-CoV papain-like protease has deISGylating and deubiquitinating activities. Virology 450–451 (2014), 64–70.
91. Minskaia, E., Hertzig, T., Gorbalenya, A.E., Campanacci, V., Cambillau, C., Canard, B., et al. Discovery of an RNA virus 3′→5′ exoribonuclease that is critically involved in coronavirus RNA synthesis. Proc. Natl. Acad. Sci. U.S.A. 103 (2006), 5108–5113.
92. Mou, H., Raj, V.S., van Kuppeveld, F.J., Rottier, P.J., Haagmans, B.L., Bosch, B.J., The receptor binding domain of the new Middle East respiratory syndrome coronavirus maps to a 231-residue region in the spike protein that efficiently elicits neutralizing antibodies. J. Virol. 87 (2013), 9379–9383.
93. Muller, M.A., van der Hoek, L., Voss, D., Bader, O., Lehmann, D., Schulz, A.R., et al. Human coronavirus NL63 open reading frame 3 encodes a virion-incorporated N-glycosylated membrane protein. Virol. J., 7, 2010, 6.
94. Muth, D., Corman, V.M., Meyer, B., Assiri, A., Al-Masri, M., Farah, M., et al. Infectious Middle East respiratory syndrome coronavirus excretion and serotype variability based on live virus isolates from patients in Saudi Arabia. J. Clin. Microbiol. 53 (2015), 2951–2955.
95. Muthumani, K., Falzarano, D., Reuschel, E.L., Tingey, C., Flingai, S., Villarreal, D.O., et al. A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates. Sci. Transl. Med., 7, 2015, 301ra132.
96. Narayanan, K., Ramirez, S.I., Lokugamage, K.G., Makino, S., Coronavirus nonstructural protein 1: common and distinct functions in the regulation of host and viral gene expression. Virus Res. 202 (2015), 89–100.
97. Netland, J., DeDiego, M.L., Zhao, J., Fett, C., Alvarez, E., Nieto-Torres, J.L., et al. Immunization with an attenuated severe acute respiratory syndrome coronavirus deleted in E protein protects against lethal respiratory disease. Virology 399 (2010), 120–128.
98. Nieto-Torres, J.L., Dediego, M.L., Verdia-Baguena, C., Jimenez-Guardeño, J.M., Regla-Nava, J.A., Fernandez-Delgado, R., et al. Severe acute respiratory syndrome coronavirus envelope protein ion channel activity promotes virus fitness and pathogenesis. PLoS Pathog., 10, 2014, e1004077.
99. Nieto-Torres, J.L., Verdia-Baguena, C., Jimenez-Guardeno, J.M., Regla-Nava, J.A., Castano-Rodriguez, C., Fernandez-Delgado, R., et al. Severe acute respiratory syndrome coronavirus E protein transports calcium ions and activates the NLRP3 inflammasome. Virology 485 (2015), 330–339.
100. Paddock, C., MERS vaccine ‘ready for human trials’. Retrieved from http://www.medicalnewstoday.com/articles/296023.php, 2015.
101. Papaneri, A.B., Johnson, R.F., Wada, J., Bollinger, L., Jahrling, P.B., Kuhn, J.H., Middle East respiratory syndrome: obstacles and prospects for vaccine development. Expert Rev. Vaccines 14 (2015), 949–962.
102. Pascal, K.E., Coleman, C.M., Mujica, A.O., Kamat, V., Badithe, A., Fairhurst, J., et al. Pre- and postexposure efficacy of fully human antibodies against Spike protein in a novel humanized mouse model of MERS-CoV infection. Proc. Natl. Acad. Sci. U.S.A. 112 (2015), 8738–8743.
103. Patterson, S., Macnaughton, M.R., Replication of human respiratory coronavirus strain 229E in human macrophages. J. Gen. Virol. 60 (1982), 307–314.
104. Peck, K.M., Cockrell, A.S., Yount, B.L., Scobey, T., Baric, R.S., Heise, M.T., Glycosylation of mouse DPP4 plays a role in inhibiting Middle East respiratory syndrome coronavirus infection. J. Virol. 89 (2015), 4696–4699.
105. Pene, F., Merlat, A., Vabret, A., Rozenberg, F., Buzyn, A., Dreyfus, F., et al. Coronavirus 229E-related pneumonia in immunocompromised patients. Clin. Infect. Dis. 37 (2003), 929–932.
106. Putics, A., Filipowicz, W., Hall, J., Gorbalenya, A.E., Ziebuhr, J., ADP-ribose-1″-monophosphatase: a conserved coronavirus enzyme that is dispensable for viral replication in tissue culture. J. Virol. 79 (2005), 12721–12731.
107. Pyrc, K., Bosch, B.J., Berkhout, B., Jebbink, M.F., Dijkman, R., Rottier, P., et al. Inhibition of human coronavirus NL63 infection at early stages of the replication cycle. Antimicrob. Agents Chemother. 50 (2006), 2000–2008.
108. Pyrc, K., Berkhout, B., van der Hoek, L., Antiviral strategies against human coronaviruses. Infect. Disord. Drug Targets 7 (2007), 59–66.
109. Ratia, K., Saikatendu, K.S., Santarsiero, B.D., Barretto, N., Baker, S.C., Stevens, R.C., et al. Severe acute respiratory syndrome coronavirus papain-like protease: structure of a viral deubiquitinating enzyme. Proc. Natl. Acad. Sci. U.S.A. 103 (2006), 5717–5722.
110. Regla-Nava, J.A., Nieto-Torres, J.L., Jimenez-Guardeno, J.M., Fernandez-Delgado, R., Fett, C., Castano-Rodriguez, C., et al. Severe acute respiratory syndrome coronaviruses with mutations in the E protein are attenuated and promising vaccine candidates. J. Virol. 89 (2015), 3870–3887.
111. Roberts, A., Deming, D., Paddock, C.D., Cheng, A., Yount, B., Vogel, L., et al. A mouse-adapted SARS-coronavirus causes disease and mortality in BALB/c mice. PLoS Pathog. 3 (2007), 23–37.
112. Roberts, A., Lamirande, E.W., Vogel, L., Baras, B., Goossens, G., Knott, I., et al. Immunogenicity and protective efficacy in mice and hamsters of a beta-propiolactone inactivated whole virus SARS-CoV vaccine. Viral Immunol. 23 (2010), 509–519.
113. Roth-Cross, J.K., Stokes, H., Chang, G., Chua, M.M., Thiel, V., Weiss, S.R., et al. Organ-specific attenuation of murine hepatitis virus strain A59 by replacement of catalytic residues in the putative viral cyclic phosphodiesterase ns2. J. Virol. 83 (2009), 3743–3753.
114. Sabir, J.S., Lam, T.T., Ahmed, M.M., Li, L., Shen, Y., Abo-Aba, S.E., et al. Co-circulation of three camel coronavirus species and recombination of MERS-CoVs in Saudi Arabia. Science 351 (2016), 81–84.
115. Scheuplein, V.A., Seifried, J., Malczyk, A.H., Miller, L., Hocker, L., Vergara-Alert, J., et al. High secretion of interferons by human plasmacytoid dendritic cells upon recognition of Middle East respiratory syndrome coronavirus. J. Virol. 89 (2015), 3859–3869.
116. Scobey, T., Yount, B.L., Sims, A.C., Donaldson, E.F., Agnihothram, S.S., Menachery, V.D., et al. Reverse genetics with a full-length infectious cDNA of the Middle East respiratory syndrome coronavirus. Proc. Natl. Acad. Sci. U.S.A. 110 (2013), 16157–16162.
117. Selinger, C., Tisoncik-Go, J., Menachery, V.D., Agnihothram, S., Law, G.L., Chang, J., et al. Cytokine systems approach demonstrates differences in innate and pro-inflammatory host responses between genetically distinct MERS-CoV isolates. BMC Genomics, 15, 2014, 1161.
118. Sheahan, T., Whitmore, A., Long, K., Ferris, M., Rockx, B., Funkhouser, W., et al. Successful vaccination strategies that protect aged mice from lethal challenge from influenza virus and heterologous severe acute respiratory syndrome coronavirus. J. Virol. 85 (2011), 217–230.
119. Shim, B.S., Stadler, K., Nguyen, H.H., Yun, C.H., Kim, D.W., Chang, J., et al. Sublingual immunization with recombinant adenovirus encoding SARS-CoV spike protein induces systemic and mucosal immunity without redirection of the virus to the brain. Virol. J., 9, 2012, 215.
120. Siu, K.L., Chan, C.P., Kok, K.H., Woo, P.C., Jin, D.Y., Comparative analysis of the activation of unfolded protein response by spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus HKU1. Cell Biosci., 4, 2014, 3.
121. Siu, K.L., Yeung, M.L., Kok, K.H., Yuen, K.S., Kew, C., Lui, P.Y., et al. Middle East respiratory syndrome coronavirus 4a protein is a double-stranded RNA-binding protein that suppresses PACT-induced activation of RIG-I and MDA5 in innate antiviral response. J. Virol. 88 (2014), 4866–4876.
122. Smith, E.C., Blanc, H., Surdel, M.C., Vignuzzi, M., Denison, M.R., Coronaviruses lacking exoribonuclease activity are susceptible to lethal mutagenesis: evidence for proofreading and potential therapeutics. PLoS Pathog., 9, 2013, e1003565.
123. Sola, I., Almazán, F., Zúñiga, S., Enjuanes, L., Continuous and discontinuous RNA synthesis in coronaviruses. Annu. Rev. Virol. 2 (2015), 265–288.
124. Song, F., Fux, R., Provacia, L.B., Volz, A., Eickmann, M., Becker, S., et al. Middle East respiratory syndrome coronavirus spike protein delivered by modified vaccinia virus Ankara efficiently induces virus-neutralizing antibodies. J. Virol. 87 (2013), 11950–11954.
125. St-Jean, J.R., Jacomy, H., Desforges, M., Vabret, A., Freymuth, F., Talbot, P.J., Human respiratory coronavirus OC43: genetic stability and neuroinvasion. J. Virol. 78 (2004), 8824–8834.
126. St-Jean, J.R., Desforges, M., Almazan, F., Jacomy, H., Enjuanes, L., Talbot, P.J., Recovery of a neurovirulent human coronavirus OC43 from an infectious cDNA clone. J. Virol. 80 (2006), 3670–3674.
127. Stobart, C.C., Moore, M.L., Development of next-generation respiratory virus vaccines through targeted modifications to viral immunomodulatory genes. Expert Rev. Vaccines 14 (2015), 1563–1572.
128. Subbarao, K., McAuliffe, J., Vogel, L., Fahle, G., Fischer, S., Tatti, K., et al. Prior infection and passive transfer of neutralizing antibody prevent replication of severe acute respiratory syndrome coronavirus in the respiratory tract of mice. J. Virol. 78 (2004), 3572–3577.
129. Sui, J., Li, W., Roberts, A., Matthews, L.J., Murakami, A., Vogel, L., et al. Evaluation of human monoclonal antibody 80R for immunoprophylaxis of severe acute respiratory syndrome by an animal study, epitope mapping, and analysis of spike variants. J. Virol. 79 (2005), 5900–5906.
130. Sui, J., Deming, M., Rockx, B., Liddington, R.C., Zhu, Q.K., Baric, R.S., et al. Effects of human anti-spike protein receptor binding domain antibodies on severe acute respiratory syndrome coronavirus neutralization escape and fitness. J. Virol. 88 (2014), 13769–13780.
131. Takaoka, A., Hayakawa, S., Yanai, H., Stoiber, D., Negishi, H., Kikuchi, H., et al. Integration of interferon-alpha/beta signalling to p53 responses in tumour suppression and antiviral defence. Nature 424 (2003), 516–523.
132. Tang, X.C., Agnihothram, S.S., Jiao, Y., Stanhope, J., Graham, R.L., Peterson, E.C., et al. Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution. Proc. Natl. Acad. Sci. U.S.A. 111 (2014), E2018–E2026.
133. Tang, J., Zhang, N., Tao, X., Zhao, G., Guo, Y., Tseng, C.T., et al. Optimization of antigen dose for a receptor-binding domain-based subunit vaccine against MERS coronavirus. Hum. Vaccin. Immunother. 11 (2015), 1244–1250.
134. Tao, X., Garron, T., Agrawal, A.S., Algaissi, A., Peng, B.H., Wakamiya, M., et al. Characterization and demonstration of the value of a lethal mouse model of Middle East Respiratory Syndrome coronavirus infection and disease. J. Virol. 90 (2015), 57–67.
135. ter Meulen, J., Bakker, A.B., van den Brink, E.N., Weverling, G.J., Martina, B.E., Haagmans, B.L., et al. Human monoclonal antibody as prophylaxis for SARS coronavirus infection in ferrets. Lancet 363 (2004), 2139–2141.
136. Thiel, V., Herold, J., Schelle, B., Siddell, S., Infectious RNA transcribed in vitro from a cDNA copy of the human coronavirus genome cloned in vaccinia virus. J. Gen. Virol. 82 (2001), 1273–1281.
137. Totura, A.L., Baric, R.S., SARS coronavirus pathogenesis: host innate immune responses and viral antagonism of interferon. Curr. Opin. Virol. 2 (2012), 264–275.
138. Tseng, C.T., Perrone, L.A., Zhu, H., Makino, S., Peters, C.J., Severe acute respiratory syndrome and the innate immune responses: modulation of effector cell function without productive infection. J. Immunol. 174 (2005), 7977–7985.
139. Tseng, C.T., Sbrana, E., Iwata-Yoshikawa, N., Newman, P.C., Garron, T., Atmar, R.L., et al. Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. PLoS One, 7, 2012, e35421.
140. van der Hoek, L., Human coronaviruses: what do they cause?. Antivir. Ther. 12 (2007), 651–658.
141. van der Hoek, L., Pyrc, K., Jebbink, M.F., Vermeulen-Oost, W., Berkhout, R.J., Wolthers, K.C., et al. Identification of a new human coronavirus. Nat. Med. 10 (2004), 368–373.
142. van der Hoek, L., Sure, K., Ihorst, G., Stang, A., Pyrc, K., Jebbink, M.F., et al. Croup is associated with the novel coronavirus NL63. PLoS Med., 2, 2005, e240.
143. van Doremalen, N., Munster, V.J., Animal models of Middle East respiratory syndrome coronavirus infection. Antivir. Res. 122 (2015), 28–38.
144. van Doremalen, N., Miazgowicz, K.L., Milne-Price, S., Bushmaker, T., Robertson, S., Scott, D., et al. Host species restriction of Middle East respiratory syndrome coronavirus through its receptor, dipeptidyl peptidase 4. J. Virol. 88 (2014), 9220–9232.
145. Varkey, J.B., Varkey, B., Viral infections in patients with chronic obstructive pulmonary disease. Curr. Opin. Pulm. Med. 14 (2008), 89–94.
146. Volz, A., Kupke, A., Song, F., Jany, S., Fux, R., Shams-Eldin, H., et al. Protective efficacy of recombinant modified vaccinia virus Ankara delivering Middle East Respiratory Syndrome coronavirus spike glycoprotein. J. Virol. 89 (2015), 8651–8656.
147. Walsh, E.E., Shin, J.H., Falsey, A.R., Clinical impact of human coronaviruses 229E and OC43 infection in diverse adult populations. J. Infect. Dis. 208 (2013), 1634–1642.
148. Wang, J., Tricoche, N., Du, L., Hunter, M., Zhan, B., Goud, G., et al. The adjuvanticity of an O. volvulus-derived rOv-ASP-1 protein in mice using sequential vaccinations and in non-human primates. PLoS One, 7, 2012, e37019.
149. Wang, S.F., Tseng, S.P., Yen, C.H., Yang, J.Y., Tsao, C.H., Shen, C.W., et al. Antibody-dependent SARS coronavirus infection is mediated by antibodies against spike proteins. Biochem. Biophys. Res. Commun. 451 (2014), 208–214.
150. Wang, L., Shi, W., Joyce, M.G., Modjarrad, K., Zhang, Y., Leung, K., et al. Evaluation of candidate vaccine approaches for MERS-CoV. Nat. Commun., 6, 2015, 7712.
151. Weingartl, H., Czub, M., Czub, S., Neufeld, J., Marszal, P., Gren, J., et al. Immunization with modified vaccinia virus Ankara-based recombinant vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in ferrets. J. Virol. 78 (2004), 12672–12676.
152. Westerbeck, J.W., Machamer, C.E., A coronavirus E protein is present in two distinct pools with different effects on assembly and the secretory pathway. J. Virol. 89 (2015), 9313–9323.
153. Woo, P.C., Lau, S.K., Chu, C.M., Chan, K.H., Tsoi, H.W., Huang, Y., et al. Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia. J. Virol. 79 (2005), 884–895.
154. Woo, P.C., Lau, S.K., Tsoi, H.W., Huang, Y., Poon, R.W., Chu, C.M., et al. Clinical and molecular epidemiological features of coronavirus HKU1-associated community-acquired pneumonia. J. Infect. Dis. 192 (2005), 1898–1907.
155. Wrensch, F., Winkler, M., Pohlmann, S., IFITM proteins inhibit entry driven by the MERS-coronavirus spike protein: evidence for cholesterol-independent mechanisms. Viruses 6 (2014), 3683–3698.
156. Yang, L.T., Peng, H., Zhu, Z.L., Li, G., Huang, Z.T., Zhao, Z.X., et al. Long-lived effector/central memory T-cell responses to severe acute respiratory syndrome coronavirus (SARS-CoV) S antigen in recovered SARS patients. Clin. Immunol. 120 (2006), 171–178.
157. Yang, Y., Zhang, L., Geng, H., Deng, Y., Huang, B., Guo, Y., et al. The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of Middle East respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists. Protein Cell 4 (2013), 951–961.
158. Yang, X., Chen, X., Bian, G., Tu, J., Xing, Y., Wang, Y., et al. Proteolytic processing, deubiquitinase and interferon antagonist activities of Middle East respiratory syndrome coronavirus papain-like protease. J. Gen. Virol. 95 (2014), 614–626.
159. Yilla, M., Harcourt, B.H., Hickman, C.J., McGrew, M., Tamin, A., Goldsmith, C.S., et al. SARS-coronavirus replication in human peripheral monocytes/macrophages. Virus Res. 107 (2005), 93–101.
160. Ying, T., Du, L., Ju, T.W., Prabakaran, P., Lau, C.C., Lu, L., et al. Exceptionally potent neutralization of Middle East respiratory syndrome coronavirus by human monoclonal antibodies. J. Virol. 88 (2014), 7796–7805.
161. Ying, T., Li, H., Lu, L., Dimitrov, D.S., Jiang, S., Development of human neutralizing monoclonal antibodies for prevention and therapy of MERS-CoV infections. Microbes Infect. 17 (2015), 142–148.
162. Ying, T., Prabakaran, P., Du, L., Shi, W., Feng, Y., Wang, Y., et al. Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody. Nat. Commun., 6, 2015, 8223.
163. Ying, T., Li, W., Dimitrov, D.S., Discovery of T-Cell infection and apoptosis by Middle East Respiratory Syndrome Coronavirus. J. Infect. Dis. 213 (2016), 877–879.
164. Yount, B., Curtis, K.M., Fritz, E.A., Hensley, L.E., Jahrling, P.B., Prentice, E., et al. Reverse genetics with a full-length infectious cDNA of severe acute respiratory syndrome coronavirus. Proc. Natl. Acad. Sci. U.S.A. 100 (2003), 12995–13000.
165. Yuan, L., Chen, Z., Song, S., Wang, S., Tian, C., Xing, G., et al. p53 degradation by a coronavirus papain-like protease suppresses type I interferon signaling. J. Biol. Chem. 290 (2015), 3172–3182.
166. Zhang, M.Y., Choudhry, V., Xiao, X., Dimitrov, D.S., Human monoclonal antibodies to the S glycoprotein and related proteins as potential therapeutics for SARS. Curr. Opin. Mol. Ther. 7 (2005), 151–156.
167. Zhang, R., Jha, B.K., Ogden, K.M., Dong, B., Zhao, L., Elliott, R., et al. Homologous 2′,5′-phosphodiesterases from disparate RNA viruses antagonize antiviral innate immunity. Proc. Natl. Acad. Sci. U.S.A. 110 (2013), 13114–13119.
168. Zhang, N., Jiang, S., Du, L., Current advancements and potential strategies in the development of MERS-CoV vaccines. Expert Rev. Vaccines 13 (2014), 761–774.
169. Zhang, R., Wang, K., Lv, W., Yu, W., Xie, S., Xu, K., et al. The ORF4a protein of human coronavirus 229E functions as a viroporin that regulates viral production. Biochim. Biophys. Acta Biomembr. 1838 (2014), 1088–1095.
170. Zhang, R., Wang, K., Ping, X., Yu, W., Qian, Z., Xiong, S., et al. The ns12.9 accessory protein of human coronavirus OC43 Is a viroporin involved in virion morphogenesis and pathogenesis. J. Virol. 89 (2015), 11383–11395.
171. Zhang, N., Channappanavar, R., Ma, C., Wang, L., Tang, J., Garron, T., et al. Identification of an ideal adjuvant for receptor-binding domain-based subunit vaccines against Middle East respiratory syndrome coronavirus. Cell. Mol. Immunol. 13 (2016), 180–190.
172. Zhao, L., Jha, B.K., Wu, A., Elliott, R., Ziebuhr, J., Gorbalenya, A.E., et al. Antagonism of the interferon-induced OAS-RNase L pathway by murine coronavirus ns2 protein is required for virus replication and liver pathology. Cell Host Microbe 11 (2012), 607–616.
173. Zhao, J., Li, K., Wohlford-Lenane, C., Agnihothram, S.S., Fett, C., Zhao, J., et al. Rapid generation of a mouse model for Middle East respiratory syndrome. Proc. Natl. Acad. Sci. U.S.A. 111 (2014), 4970–4975.
174. Zhao, X., Guo, F., Liu, F., Cuconati, A., Chang, J., Block, T.M., et al. Interferon induction of IFITM proteins promotes infection by human coronavirus OC43. Proc. Natl. Acad. Sci. U.S.A. 111 (2014), 6756–6761.
175. Zhao, G., Jiang, Y., Qiu, H., Gao, T., Zeng, Y., Guo, Y., et al. Multi-organ damage in human dipeptidyl peptidase 4 transgenic mice infected with Middle East respiratory syndrome-coronavirus. PLoS One, 10, 2015, e0145561.
176. Zhao, J., Perera, R.A., Kayali, G., Meyerholz, D., Perlman, S., Peiris, M., Passive immunotherapy with dromedary immune serum in an experimental animal model for Middle East respiratory syndrome coronavirus infection. J. Virol. 89 (2015), 6117–6120.
177. Zheng, D., Chen, G., Guo, B., Cheng, G., Tang, H., PLP2, a potent deubiquitinase from murine hepatitis virus, strongly inhibits cellular type I interferon production. Cell Res. 18 (2008), 1105–1113.
178. Zhong, Y., Tan, Y.W., Liu, D.X., Recent progress in studies of arterivirus- and coronavirus-host interactions. Viruses 4 (2012), 980–1010.
179. Zhou, P., Han, Z., Wang, L.F., Shi, Z., Identification of immunogenic determinants of the spike protein of SARS-like coronavirus. Virol. Sin. 28 (2013), 92–96.
180. Zhou, W., Wang, W., Wang, H., Lu, R., Tan, W., First infection by all four non-severe acute respiratory syndrome human coronaviruses takes place during childhood. BMC Infect. Dis., 13, 2013, 433.
181. Zhou, J., Chu, H., Li, C., Wong, B.H., Cheng, Z.S., Poon, V.K., et al. Active replication of Middle East respiratory syndrome coronavirus and aberrant induction of inflammatory cytokines and chemokines in human macrophages: implications for pathogenesis. J. Infect. Dis. 209 (2014), 1331–1342.
182. Zhou, J., Chu, H., Chan, J.F., Yuen, K.Y., Middle East respiratory syndrome coronavirus infection: virus-host cell interactions and implications on pathogenesis. Virol. J., 12, 2015, 218.
183. Zhu, Z., Chakraborti, S., He, Y., Roberts, A., Sheahan, T., Xiao, X., et al. Potent cross-reactive neutralization of SARS coronavirus isolates by human monoclonal antibodies. Proc. Natl. Acad. Sci. U.S.A. 104 (2007), 12123–12128.
184. Ziebuhr, J., The coronavirus replicase. Enjuanes, L., (eds.) Coronavirus Replication and Reverse Genetics, vol. 287, 2005, Springer-Verlag, Berlin, Heidelberg, 57–94.
185. Ziegler, T., Matikainen, S., Ronkko, E., Osterlund, P., Sillanpaa, M., Siren, J., et al. Severe acute respiratory syndrome coronavirus fails to activate cytokine-mediated innate immune responses in cultured human monocyte-derived dendritic cells. J. Virol. 79 (2005), 13800–13805.
186. Zielecki, F., Weber, M., Eickmann, M., Spiegelberg, L., Zaki, A.M., Matrosovich, M., et al. Human cell tropism and innate immune system interactions of human respiratory coronavirus EMC compared to those of severe acute respiratory syndrome coronavirus. J. Virol. 87 (2013), 5300–5304.
187. Zumla, A., Chan, J.F., Azhar, E.I., Hui, D.S., Yuen, K.Y., Coronaviruses—drug discovery and therapeutic options. Nat. Rev. Drug Discov. 15 (2016), 327–347.
188. Zust, R., Cervantes-Barragan, L., Kuri, T., Blakqori, G., Weber, F., Ludewig, B., et al. Coronavirus non-structural protein 1 is a major pathogenicity factor: implications for the rational design of coronavirus vaccines. PLoS Pathog., 3, 2007, e109.
189. Zust, R., Cervantes-Barragan, L., Habjan, M., Maier, R., Neuman, B.W., Ziebuhr, J., et al. Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5. Nat. Immunol. 12 (2011), 137–143.