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Abstract

The coronavirus spike protein is a multifunctional molecular machine that mediates coronavirus entry into host cells. It first binds to a receptor on the host cell surface through its S1 subunit and then fuses viral and host membranes through its S2 subunit. Two domains in S1 from different coronaviruses recognize a variety of host receptors, leading to viral attachment. The spike protein exists in two structurally distinct conformations, prefusion and postfusion. The transition from prefusion to postfusion conformation of the spike protein must be triggered, leading to membrane fusion. This article reviews current knowledge about the structures and functions of coronavirus spike proteins, illustrating how the two S1 domains recognize different receptors and how the spike proteins are regulated to undergo conformational transitions. I further discuss the evolution of these two critical functions of coronavirus spike proteins, receptor recognition and membrane fusion, in the context of the corresponding functions from other viruses and host cells.

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2016-09-29
2024-03-28
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Literature Cited

  1. Ksiazek TG, Erdman D, Goldsmith CS, Zaki SR, Peret T. 1.  et al. 2003. A novel coronavirus associated with severe acute respiratory syndrome. N. Engl. J. Med. 348:1953–66 [Google Scholar]
  2. Peiris JSM, Lai ST, Poon LLM, Guan Y, Yam LYC. 2.  et al. 2003. Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet 361:1319–25 [Google Scholar]
  3. Marra MA, Jones SJM, Astell CR, Holt RA, Brooks-Wilson A. 3.  et al. 2003. The genome sequence of the SARS-associated coronavirus. Science 300:1399–404 [Google Scholar]
  4. Rota PA, Oberste MS, Monroe SS, Nix WA, Campagnoli R. 4.  et al. 2003. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science 300:1394–99 [Google Scholar]
  5. Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus A, Fouchier RAM. 5.  2012. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N. Engl. J. Med. 367:1814–20 [Google Scholar]
  6. de Groot RJ, Baker SC, Baric RS, Brown CS, Drosten C. 6.  et al. 2013. Middle East respiratory syndrome coronavirus (MERS-CoV): announcement of the Coronavirus Study Group. J. Virol. 87:7790–92 [Google Scholar]
  7. Mole B. 7.  2013. Deadly pig virus slips through US borders. Nature 499:388 [Google Scholar]
  8. Stevenson GW, Hoang H, Schwartz KJ, Burrough ER, Sun D. 8.  et al. 2013. Emergence of porcine epidemic diarrhea virus in the United States: clinical signs, lesions, and viral genomic sequences. J. Vet. Diagn. Investig. 25:649–54 [Google Scholar]
  9. Chen Q, Li G, Stasko J, Thomas JT, Stensland WR. 9.  et al. 2014. Isolation and characterization of porcine epidemic diarrhea viruses associated with the 2013 disease outbreak among swine in the United States. J. Clin. Microbiol. 52:234–43 [Google Scholar]
  10. Enjuanes L, Almazan F, Sola I, Zuniga S. 10.  2006. Biochemical aspects of coronavirus replication and virus-host interaction. Annu. Rev. Microbiol. 60:211–30 [Google Scholar]
  11. Perlman S, Netland J. 11.  2009. Coronaviruses post-SARS: update on replication and pathogenesis. Nat. Rev. Microbiol. 7:439–50 [Google Scholar]
  12. Graham RL, Baric RS. 12.  2010. Recombination, reservoirs, and the modular spike: mechanisms of coronavirus cross-species transmission. J. Virol. 84:3134–46 [Google Scholar]
  13. Li F. 13.  2013. Receptor recognition and cross-species infections of SARS coronavirus. Antivir. Res. 100:246–54 [Google Scholar]
  14. Li WH, Wong SK, Li F, Kuhn JH, Huang IC. 14.  et al. 2006. Animal origins of the severe acute respiratory syndrome coronavirus: insight from ACE2–S-protein interactions. J. Virol. 80:4211–19 [Google Scholar]
  15. Kirchdoerfer RN, Cottrell CA, Wang N, Pallesen J, Yassine HM. 15.  et al. 2016. Pre-fusion structure of a human coronavirus spike protein. Nature 531:118–21 [Google Scholar]
  16. Walls AC, Tortorici MA, Bosch BJ, Frenz B, Rottier PJ. 16.  et al. 2016. Cryo-electron microscopy structure of a coronavirus spike glycoprotein trimer. Nature 531:114–17 [Google Scholar]
  17. Beniac DR, Andonov A, Grudeski E, Booth TF. 17.  2006. Architecture of the SARS coronavirus prefusion spike. Nat. Struct. Mol. Biol. 13:751–52 [Google Scholar]
  18. Li F, Berardi M, Li WH, Farzan M, Dormitzer PR, Harrison SC. 18.  2006. Conformational states of the severe acute respiratory syndrome coronavirus spike protein ectodomain. J. Virol. 80:6794–800 [Google Scholar]
  19. Li F. 19.  2015. Receptor recognition mechanisms of coronaviruses: a decade of structural studies. J. Virol. 89:1954–64 [Google Scholar]
  20. Li WH, Moore MJ, Vasilieva N, Sui JH, Wong SK. 20.  et al. 2003. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426:450–54 [Google Scholar]
  21. Hofmann H, Pyrc K, van der Hoek L, Geier M, Berkhout B, Pohlmann S. 21.  2005. Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry. PNAS 102:7988–93 [Google Scholar]
  22. Delmas B, Gelfi J, Lharidon R, Vogel LK, Sjostrom H. 22.  et al. 1992. Aminopeptidase-N is a major receptor for the enteropathogenic coronavirus TGEV. Nature 357:417–20 [Google Scholar]
  23. Liu C, Tang J, Ma Y, Liang X, Yang Y. 23.  et al. 2015. Receptor usage and cell entry of porcine epidemic diarrhea coronavirus. J. Virol. 89:6121–25 [Google Scholar]
  24. Li BX, Ge JW, Li YJ. 24.  2007. Porcine aminopeptidase N is a functional receptor for the PEDV coronavirus. Virology 365:166–72 [Google Scholar]
  25. Delmas B, Gelfi J, Sjostrom H, Noren O, Laude H. 25.  1993. Further characterization of aminopeptidase-N as a receptor for coronaviruses. Adv. Exp. Med. Biol. 342:293–98 [Google Scholar]
  26. Raj VS, Mou HH, Smits SL, Dekkers DHW, Muller MA. 26.  et al. 2013. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature 495:251–54 [Google Scholar]
  27. Yang Y, Du L, Liu C, Wang L, Ma C. 27.  et al. 2014. Receptor usage and cell entry of bat coronavirus HKU4 provide insight into bat-to-human transmission of MERS coronavirus. PNAS 111:12516–21 [Google Scholar]
  28. Dveksler GS, Pensiero MN, Cardellichio CB, Williams RK, Jiang GS. 28.  et al. 1991. Cloning of the mouse hepatitis-virus (MHV) receptor: expression in human and hamster cell lines confers susceptibility to MHV. J. Virol. 65:6881–91 [Google Scholar]
  29. Williams RK, Jiang GS, Holmes KV. 29.  1991. Receptor for mouse hepatitis virus is a member of the carcinoembryonic antigen family of glycoproteins. PNAS 88:5533–36 [Google Scholar]
  30. Schultze B, Gross HJ, Brossmer R, Herrler G. 30.  1991. The S protein of bovine coronavirus is a hemagglutinin recognizing 9-O-acetylated sialic acid as a receptor determinant. J. Virol. 65:6232–37 [Google Scholar]
  31. Schultze B, Cavanagh D, Herrler G. 31.  1992. Neuraminidase treatment of avian infectious bronchitis coronavirus reveals a hemagglutinating activity that is dependent on sialic acid–containing receptors on erythrocytes. Virology 189:792–94 [Google Scholar]
  32. Cavanagh D, Davis PJ. 32.  1986. Coronavirus IBV: removal of spike glycopolypeptide S1 by urea abolishes infectivity and hemagglutination but not attachment to cells. J. Gen. Virol. 67:1443–48 [Google Scholar]
  33. Schwegmann-Wessels C, Herrler G. 33.  2006. Sialic acids as receptor determinants for coronaviruses. Glycoconj. J. 23:51–58 [Google Scholar]
  34. Krempl C, Schultze B, Laude H, Herrler G. 34.  1997. Point mutations in the S protein connect the sialic acid binding activity with the enteropathogenicity of transmissible gastroenteritis coronavirus. J. Virol. 71:3285–87 [Google Scholar]
  35. Liu C, Yang Y, Chen L, Lin YL, Li F. 35.  2014. A unified mechanism for aminopeptidase N–based tumor cell motility and tumor-homing therapy. J. Biol. Chem. 289:34520–29 [Google Scholar]
  36. Mina-Osorio P. 36.  2008. The moonlighting enzyme CD13: old and new functions to target. Trends Mol. Med. 14:361–71 [Google Scholar]
  37. Boehm M, Nabel EG. 37.  2002. Angiotensin-converting enzyme 2—a new cardiac regulator. N. Engl. J. Med. 347:1795–97 [Google Scholar]
  38. Kameoka J, Tanaka T, Nojima Y, Schlossman SF, Morimoto C. 38.  1993. Direct association of adenosine deaminase with a T cell activation antigen, CD26. Science 261:466–69 [Google Scholar]
  39. Wesley UV, McGroarty M, Homoyouni A. 39.  2005. Dipeptidyl peptidase inhibits malignant phenotype of prostate cancer cells by blocking basic fibroblast growth factor signaling pathway. Cancer Res. 65:1325–34 [Google Scholar]
  40. Hammarstrom S. 40.  1999. The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues. Semin. Cancer Biol. 9:67–81 [Google Scholar]
  41. Dove A. 41.  2001. The bittersweet promise of glycobiology. Nat. Biotechnol. 19:913–17 [Google Scholar]
  42. Li F. 42.  2012. Evidence for a common evolutionary origin of coronavirus spike protein receptor-binding subunits. J. Virol. 86:2856–58 [Google Scholar]
  43. Peng GQ, Xu LQ, Lin YL, Chen L, Pasquarella JR. 43.  et al. 2012. Crystal structure of bovine coronavirus spike protein lectin domain. J. Biol. Chem. 287:41931–38 [Google Scholar]
  44. Promkuntod N, van Eijndhoven RE, de Vrieze G, Grone A, Verheije MH. 44.  2014. Mapping of the receptor-binding domain and amino acids critical for attachment in the spike protein of avian coronavirus infectious bronchitis virus. Virology 448:26–32 [Google Scholar]
  45. Kubo H, Yamada YK, Taguchi F. 45.  1994. Localization of neutralizing epitopes and the receptor-binding site within the amino-terminal 330 amino-acids of the murine coronavirus spike protein. J. Virol. 68:5403–10 [Google Scholar]
  46. Wong SK, Li WH, Moore MJ, Choe H, Farzan M. 46.  2004. A 193–amino acid fragment of the SARS coronavirus S protein efficiently binds angiotensin-converting enzyme 2. J. Biol. Chem. 279:3197–201 [Google Scholar]
  47. Lin HX, Fen Y, Wong G, Wang LP, Li B. 47.  et al. 2008. Identification of residues in the receptor-binding domain (RBD) of the spike protein of human coronavirus NL63 that are critical for the RBD–ACE2 receptor interaction. J. Gen. Virol. 89:1015–24 [Google Scholar]
  48. Hofmann H, Simmons G, Rennekamp AJ, Chaipan C, Gramberg T. 48.  et al. 2006. Highly conserved regions within the spike proteins of human coronaviruses 229E and NL63 determine recognition of their respective cellular receptors. J. Virol. 80:8639–52 [Google Scholar]
  49. Godet M, Grosclaude J, Delmas B, Laude H. 49.  1994. Major receptor-binding and neutralization determinants are located within the same domain of the transmissible gastroenteritis virus (coronavirus) spike protein. J. Virol. 68:8008–16 [Google Scholar]
  50. Du L, Zhao G, Kou Z, Ma C, Sun S. 50.  et al. 2013. Identification of a receptor-binding domain in the S protein of the novel human coronavirus Middle East respiratory syndrome coronavirus as an essential target for vaccine development. J. Virol. 87:9939–42 [Google Scholar]
  51. Mou H, Raj VS, van Kuppeveld FJ, Rottier PJ, Haagmans BL, Bosch BJ. 51.  2013. The receptor binding domain of the new MERS coronavirus maps to a 231-residue region in the spike protein that efficiently elicits neutralizing antibodies. J. Virol. In press doi: 10.1128/JVI.01277-13 [Google Scholar]
  52. Li F, Li WH, Farzan M, Harrison SC. 52.  2005. Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science 309:1864–68 [Google Scholar]
  53. Li F, Li WH, Farzan M, Harrison SC. 53.  2006. Interactions between SARS coronavirus and its receptor. Nidoviruses: Toward Control of SARS and Other Nidovirus Diseases S Perlman, KV Holmes 229–34 New York: Springer [Google Scholar]
  54. Towler P, Staker B, Prasad SG, Menon S, Tang J. 54.  et al. 2004. ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis. J. Biol. Chem. 279:17996–8007 [Google Scholar]
  55. Li WH, Zhang CS, Sui JH, Kuhn JH, Moore MJ. 55.  et al. 2005. Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2. EMBO J. 24:1634–43 [Google Scholar]
  56. Guan Y, Zheng BJ, He YQ, Liu XL, Zhuang ZX. 56.  et al. 2003. Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China. Science 302:276–78 [Google Scholar]
  57. Li F. 57.  2008. Structural analysis of major species barriers between humans and palm civets for severe acute respiratory syndrome coronavirus infections. J. Virol. 82:6984–91 [Google Scholar]
  58. Wu KL, Peng GQ, Wilken M, Geraghty RJ, Li F. 58.  2012. Mechanisms of host receptor adaptation by severe acute respiratory syndrome coronavirus. J. Biol. Chem. 287:8904–11 [Google Scholar]
  59. Wu K, Chen L, Peng G, Zhou W, Pennell CA. 59.  et al. 2011. A virus-binding hot spot on human angiotensin-converting enzyme 2 is critical for binding of two different coronaviruses. J. Virol. 85:5331–37 [Google Scholar]
  60. Song HD, Tu CC, Zhang GW, Wang SY, Zheng K. 60.  et al. 2005. Cross-host evolution of severe acute respiratory syndrome coronavirus in palm civet and human. PNAS 102:2430–35 [Google Scholar]
  61. Qu XX, Hao P, Song XJ, Jiang SM, Liu YX. 61.  et al. 2005. Identification of two critical amino acid residues of the severe acute respiratory syndrome coronavirus spike protein for its variation in zoonotic tropism transition via a double substitution strategy. J. Biol. Chem. 280:29588–95 [Google Scholar]
  62. Li WH, Greenough TC, Moore MJ, Vasilieva N, Somasundaran M. 62.  et al. 2004. Efficient replication of severe acute respiratory syndrome coronavirus in mouse cells is limited by murine angiotensin-converting enzyme 2. J. Virol. 78:11429–33 [Google Scholar]
  63. Frieman M, Yount B, Agnihothram S, Page C, Donaldson E. 63.  et al. 2012. Molecular determinants of severe acute respiratory syndrome coronavirus pathogenesis and virulence in young and aged mouse models of human disease. J. Virol. 86:884–97 [Google Scholar]
  64. Ge XY, Li JL, Yang XL, Chmura AA, Zhu G. 64.  et al. 2013. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Nature 503:535–38 [Google Scholar]
  65. Menachery VD, Yount BL Jr, Debbink K, Agnihothram S, Gralinski LE. 65.  et al. 2015. A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. Nat. Med. 21:1508–13 [Google Scholar]
  66. Li WD, Shi ZL, Yu M, Ren WZ, Smith C. 66.  et al. 2005. Bats are natural reservoirs of SARS-like coronaviruses. Science 310:676–79 [Google Scholar]
  67. Lau SKP, Woo PCY, Li KSM, Huang Y, Tsoi HW. 67.  et al. 2005. Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats. PNAS 102:14040–45 [Google Scholar]
  68. Hou YX, Peng C, Yu M, Li Y, Han ZG. 68.  et al. 2010. Angiotensin-converting enzyme 2 (ACE2) proteins of different bat species confer variable susceptibility to SARS-CoV entry. Arch. Virol. 155:1563–69 [Google Scholar]
  69. Lu G, Hu Y, Wang Q, Qi J, Gao F. 69.  et al. 2013. Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26. Nature 500:227–31 [Google Scholar]
  70. Wang N, Shi X, Jiang L, Zhang S, Wang D. 70.  et al. 2013. Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4. Cell Res. 23:986–93 [Google Scholar]
  71. Chen Y, Rajashankar KR, Yang Y, Agnihothram SS, Liu C. 71.  et al. 2013. Crystal structure of the receptor-binding domain from newly emerged Middle East respiratory syndrome coronavirus. J. Virol. 87:10777–83 [Google Scholar]
  72. Rasmussen HB, Branner S, Wiberg FC, Wagtmann N. 72.  2003. Crystal structure of human dipeptidyl peptidase IV/CD26 in complex with a substrate analog. Nat. Struct. Biol. 10:19–25 [Google Scholar]
  73. Peck KM, Cockrell AS, Yount BL, Scobey T, Baric RS, Heise MT. 73.  2015. Glycosylation of mouse DPP4 plays a role in inhibiting Middle East respiratory syndrome coronavirus infection. J. Virol. 89:4696–99 [Google Scholar]
  74. Cockrell AS, Peck KM, Yount BL, Agnihothram SS, Scobey T. 74.  et al. 2014. Mouse dipeptidyl peptidase 4 is not a functional receptor for Middle East respiratory syndrome coronavirus infection. J. Virol. 88:5195–99 [Google Scholar]
  75. Fukuma A, Tani H, Taniguchi S, Shimojima M, Saijo M, Fukushi S. 75.  2015. Inability of rat DPP4 to allow MERS-CoV infection revealed by using a VSV pseudotype bearing truncated MERS-CoV spike protein. Arch. Virol. 160:2293–300 [Google Scholar]
  76. Barlan A, Zhao J, Sarkar MK, Li K, McCray PB Jr. 76.  2014. Receptor variation and susceptibility to Middle East respiratory syndrome coronavirus infection. J. Virol. 88:4953–61 [Google Scholar]
  77. Haagmans BL, Al Dhahiry SH, Reusken CB, Raj VS, Galiano M. 77.  et al. 2014. Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation. Lancet Infect. Dis. 14:140–45 [Google Scholar]
  78. Alagaili AN, Briese T, Mishra N, Kapoor V, Sameroff SC. 78.  et al. 2014. Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia. mBio 5:e00884–14 [Google Scholar]
  79. Annan A, Baldwin HJ, Corman VM, Klose SM, Owusu M. 79.  et al. 2013. Human β-coronavirus 2c EMC/2012-related viruses in bats, Ghana and Europe. Emerg. Infect. Dis. 19:456–59 [Google Scholar]
  80. Holmes KV, Dominguez SR. 80.  2013. The new age of virus discovery: genomic analysis of a novel human β-coronavirus isolated from a fatal case of pneumonia. mBio 4:e00548–12 [Google Scholar]
  81. Lau SK, Li KS, Tsang AK, Lam CS, Ahmed S. 81.  et al. 2013. Genetic characterization of Betacoronavirus lineage C viruses in bats reveals marked sequence divergence in the spike protein of Pipistrellus bat coronavirus HKU5 in Japanese pipistrelle: implications for the origin of the novel Middle East respiratory syndrome coronavirus. J. Virol. 87:8638–50 [Google Scholar]
  82. Wang Q, Qi J, Yuan Y, Xuan Y, Han P. 82.  et al. 2014. Bat origins of MERS-CoV supported by bat coronavirus HKU4 usage of human receptor CD26. Cell Host Microbe 16:328–37 [Google Scholar]
  83. Wu K, Li W, Peng G, Li F. 83.  2009. Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor. PNAS 106:19970–74 [Google Scholar]
  84. Reguera J, Santiago C, Mudgal G, Ordono D, Enjuanes L, Casasnovas JM. 84.  2012. Structural bases of coronavirus attachment to host aminopeptidase N and its inhibition by neutralizing antibodies. PLOS Pathog. 8:e1002859 [Google Scholar]
  85. Chen L, Lin YL, Peng G, Li F. 85.  2012. Structural basis for multifunctional roles of mammalian aminopeptidase N. PNAS 109:17966–71 [Google Scholar]
  86. Wong AH, Zhou D, Rini JM. 86.  2012. The X-ray crystal structure of human aminopeptidase N reveals a novel dimer and the basis for peptide processing. J. Biol. Chem. 287:36804–13 [Google Scholar]
  87. Tusell SM, Schittone SA, Holmes KV. 87.  2007. Mutational analysis of aminopeptidase N, a receptor for several group 1 coronaviruses, identifies key determinants of viral host range. J. Virol. 81:1261–73 [Google Scholar]
  88. Peng GQ, Sun DW, Rajashankar KR, Qian ZH, Holmes KV, Li F. 88.  2011. Crystal structure of mouse coronavirus receptor-binding domain complexed with its murine receptor. PNAS 108:10696–701 [Google Scholar]
  89. Beauchemin N, Draber P, Dveksler G, Gold P, Gray-Owen S. 89.  et al. 1999. Redefined nomenclature for members of the carcinoembryonic antigen family. Exp. Cell Res. 252:243–49 [Google Scholar]
  90. Tan KM, Zelus BD, Meijers R, Liu JH, Bergelson JM. 90.  et al. 2002. Crystal structure of murine sCEACAM1a[1,4]: a coronavirus receptor in the CEA family. EMBO J. 21:2076–86 [Google Scholar]
  91. Wessner DR, Shick PC, Lu JH, Cardellichio CB, Gagneten SE. 91.  et al. 1998. Mutational analysis of the virus and monoclonal antibody binding sites in MHVR, the cellular receptor of the murine coronavirus mouse hepatitis virus strain A59. J. Virol. 72:1941–48 [Google Scholar]
  92. Thackray LB, Turner BC, Holmes KV. 92.  2005. Substitutions of conserved amino acids in the receptor-binding domain of the spike glycoprotein affect utilization of murine CEACAM1a by the murine coronavirus MHV-A59. Virology 334:98–110 [Google Scholar]
  93. Leparc-Goffart I, Hingley ST, Chua MM, Jiang XH, Lavi E, Weiss SR. 93.  1997. Altered pathogenesis of a mutant of the murine coronavirus MHV-A59 is associated with a Q159L amino acid substitution in the spike protein. Virology 239:1–10 [Google Scholar]
  94. Tsai JC, Zelus BD, Holmes KV, Weiss SR. 94.  2003. The N-terminal domain of the murine coronavirus spike glycoprotein determines the CEACAM1 receptor specificity of the virus strain. J. Virol. 77:841–50 [Google Scholar]
  95. Ohtsuka N, Taguchi F. 95.  1997. Mouse susceptibility to mouse hepatitis virus infection is linked to viral receptor genotype. J. Virol. 71:8860–63 [Google Scholar]
  96. Ohtsuka N, Yamada YK, Taguchi F. 96.  1996. Difference in virus-binding activity of two distinct receptor proteins for mouse hepatitis virus. J. Gen. Virol. 77:1683–92 [Google Scholar]
  97. Hirai A, Ohtsuka N, Ikeda T, Taniguchi R, Blau D. 97.  et al. 2010. Role of mouse hepatitis virus (MHV) receptor murine CEACAM1 in the resistance of mice to MHV infection: studies of mice with chimeric mCEACAM1a and mCEACAM1b. J. Virol. 84:6654–66 [Google Scholar]
  98. Seetharaman J, Kanigsberg A, Slaaby R, Leffler H, Barondes SH, Rini JM. 98.  1998. X-ray crystal structure of the human galectin-3 carbohydrate recognition domain at 2.1-Å resolution. J. Biol. Chem. 273:13047–52 [Google Scholar]
  99. Kunkel F, Herrler G. 99.  1993. Structural and functional-analysis of the surface protein of human coronavirus OC43. Virology 195:195–202 [Google Scholar]
  100. Vijgen L, Keyaerts E, Lemey P, Maes P, van Reeth K. 100.  et al. 2006. Evolutionary history of the closely related group 2 coronaviruses: porcine hemagglutinating encephalomyelitis virus, bovine coronavirus, and human coronavirus OC43. J. Virol. 80:7270–74 [Google Scholar]
  101. Vijgen L, Keyaerts E, Moes E, Thoelen I, Wollants E. 101.  et al. 2005. Complete genomic sequence of human coronavirus OC43: molecular clock analysis suggests a relatively recent zoonotic coronavirus transmission event. J. Virol. 79:1595–604 [Google Scholar]
  102. Klein A, Krishna M, Varki NM, Varki A. 102.  1994. 9-O-acetylated sialic acids have widespread but selective expression: analysis using a chimeric dual-function probe derived from influenza C hemagglutinin-esterase. PNAS 91:7782–86 [Google Scholar]
  103. Chen L, Li F. 103.  2013. Structural analysis of the evolutionary origins of influenza virus hemagglutinin and other viral lectins. J. Virol. 87:4118–20 [Google Scholar]
  104. Eckert DM, Kim PS. 104.  2001. Mechanisms of viral membrane fusion and its inhibition. Annu. Rev. Biochem. 70:777–810 [Google Scholar]
  105. Skehel JJ, Wiley DC. 105.  2000. Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annu. Rev. Biochem. 69:531–69 [Google Scholar]
  106. Klenk HD, Garten W. 106.  1994. Host cell proteases controlling virus pathogenicity. Trends Microbiol 2:39–43 [Google Scholar]
  107. Wilson IA, Skehel JJ, Wiley DC. 107.  1981. Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 Å resolution. Nature 289:366–73 [Google Scholar]
  108. Stein BS, Gowda SD, Lifson JD, Penhallow RC, Bensch KG, Engleman EG. 108.  1987. pH-independent HIV entry into CD4-positive T cells via virus envelope fusion to the plasma membrane. Cell 49:659–68 [Google Scholar]
  109. White J, Matlin K, Helenius A. 109.  1981. Cell fusion by Semliki Forest, influenza, and vesicular stomatitis viruses. J. Cell Biol. 89:674–79 [Google Scholar]
  110. Mothes W, Boerger AL, Narayan S, Cunningham JM, Young JA. 110.  2000. Retroviral entry mediated by receptor priming and low pH triggering of an envelope glycoprotein. Cell 103:679–89 [Google Scholar]
  111. Belouzard S, Millet JK, Licitra BN, Whittaker GR. 111.  2012. Mechanisms of coronavirus cell entry mediated by the viral spike protein. Viruses 4:1011–33 [Google Scholar]
  112. Heald-Sargent T, Gallagher T. 112.  2012. Ready, set, fuse! The coronavirus spike protein and acquisition of fusion competence. Viruses 4:557–80 [Google Scholar]
  113. Xu YH, Lou ZY, Liu YW, Pang H, Tien P. 113.  et al. 2004. Crystal structure of severe acute respiratory syndrome coronavirus spike protein fusion core. J. Biol. Chem. 279:49414–19 [Google Scholar]
  114. Lu L, Liu Q, Zhu Y, Chan KH, Qin L. 114.  et al. 2014. Structure-based discovery of Middle East respiratory syndrome coronavirus fusion inhibitor. Nat. Commun. 5:3067 [Google Scholar]
  115. Zheng Q, Deng Y, Liu J, van der Hoek L, Berkhout B, Lu M. 115.  2006. Core structure of S2 from the human coronavirus NL63 spike glycoprotein. Biochemistry 45:15205–15 [Google Scholar]
  116. Xu Y, Liu Y, Lou Z, Qin L, Li X. 116.  et al. 2004. Structural basis for coronavirus-mediated membrane fusion. Crystal structure of mouse hepatitis virus spike protein fusion core. J. Biol. Chem. 279:30514–22 [Google Scholar]
  117. Duquerroy S, Vigouroux AN, Rottier PJM, Rey FA, Bosch BJ. 117.  2005. Central ions and lateral asparagine/glutamine zippers stabilize the post-fusion hairpin conformation of the SARS coronavirus spike glycoprotein. Virology 335:276–85 [Google Scholar]
  118. Gao J, Lu G, Qi J, Li Y, Wu Y. 118.  et al. 2013. Structure of the fusion core and inhibition of fusion by a heptad repeat peptide derived from the S protein of Middle East respiratory syndrome coronavirus. J. Virol. 87:13134–40 [Google Scholar]
  119. Supekar VM, Bruckmann C, Ingallinella P, Bianchi E, Pessi A, Carfi A. 119.  2004. Structure of a proteolytically resistant core from the severe acute respiratory syndrome coronavirus S2 fusion protein. PNAS 101:17958–63 [Google Scholar]
  120. Millet JK, Whittaker GR. 120.  2015. Host cell proteases: critical determinants of coronavirus tropism and pathogenesis. Virus Res 202:120–34 [Google Scholar]
  121. Spaan W, Cavanagh D, Horzinek MC. 121.  1988. Coronaviruses: structure and genome expression. J. Gen. Virol. 69:2939–52 [Google Scholar]
  122. Matsuyama S, Taguchi F. 122.  2002. Receptor-induced conformational changes of murine coronavirus spike protein. J. Virol. 76:11819–26 [Google Scholar]
  123. Zelus BD, Schickli JH, Blau DM, Weiss SR, Holmes KV. 123.  2003. Conformational changes in the spike glycoprotein of murine coronavirus are induced at 37°C either by soluble murine CEACAM1 receptors or by pH 8. J. Virol. 77:830–40 [Google Scholar]
  124. Qiu Z, Hingley ST, Simmons G, Yu C, Das Sarma J. 124.  et al. 2006. Endosomal proteolysis by cathepsins is necessary for murine coronavirus mouse hepatitis virus type 2 spike-mediated entry. J. Virol. 80:5768–76 [Google Scholar]
  125. Eifart P, Ludwig K, Bottcher C, de Haan CA, Rottier PJ. 125.  et al. 2007. Role of endocytosis and low pH in murine hepatitis virus strain A59 cell entry. J. Virol. 81:10758–68 [Google Scholar]
  126. Nakagaki K, Nakagaki K, Taguchi F. 126.  2005. Receptor-independent spread of a highly neurotropic murine coronavirus JHMV strain from initially infected microglial cells in mixed neural cultures. J. Virol. 79:6102–10 [Google Scholar]
  127. Gallagher TM, Buchmeier MJ, Perlman S. 127.  1992. Cell receptor–independent infection by a neurotropic murine coronavirus. Virology 191:517–22 [Google Scholar]
  128. Taguchi F, Matsuyama S, Saeki K. 128.  1999. Difference in Bgp-independent fusion activity among mouse hepatitis viruses. Arch. Virol. 144:2041–49 [Google Scholar]
  129. Krueger DK, Kelly SM, Lewicki DN, Ruffolo R, Gallagher TM. 129.  2001. Variations in disparate regions of the murine coronavirus spike protein impact the initiation of membrane fusion. J. Virol. 75:2792–802 [Google Scholar]
  130. Ontiveros E, Kim TS, Gallagher TM, Perlman S. 130.  2003. Enhanced virulence mediated by the murine coronavirus, mouse hepatitis virus strain JHM, is associated with a glycine at residue 310 of the spike glycoprotein. J. Virol. 77:10260–69 [Google Scholar]
  131. Miura TA, Travanty EA, Oko L, Bielefeldt-Ohmann H, Weiss SR. 131.  et al. 2008. The spike glycoprotein of murine coronavirus MHV-JHM mediates receptor-independent infection and spread in the central nervous systems of Ceacam1a−/− mice. J. Virol. 82:755–63 [Google Scholar]
  132. Phillips JM, Weiss SR. 132.  2011. Pathogenesis of neurotropic murine coronavirus is multifactorial. Trends Pharmacol. Sci. 32:2–7 [Google Scholar]
  133. Song HC, Seo MY, Stadler K, Yoo BJ, Choo QL. 133.  et al. 2004. Synthesis and characterization of a native, oligomeric form of recombinant severe acute respiratory syndrome coronavirus spike glycoprotein. J. Virol. 78:10328–35 [Google Scholar]
  134. Xiao X, Chakraborti S, Dimitrov AS, Gramatikoff K, Dimitrov DS. 134.  2003. The SARS-CoV S glycoprotein: expression and functional characterization. Biochem. Biophys. Res. Commun. 312:1159–64 [Google Scholar]
  135. Simmons G, Gosalia DN, Rennekamp AJ, Reeves JD, Diamond SL, Bates P. 135.  2005. Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry. PNAS 102:11876–81 [Google Scholar]
  136. Simmons G, Reeves JD, Rennekamp AJ, Amberg SM, Piefer AJ, Bates P. 136.  2004. Characterization of severe acute respiratory syndrome–associated coronavirus (SARS-CoV) spike glycoprotein-mediated viral entry. PNAS 101:4240–45 [Google Scholar]
  137. Huang IC, Bosch BJ, Li F, Li WH, Lee KH. 137.  et al. 2006. SARS coronavirus, but not human coronavirus NL63, utilizes cathepsin L to infect ACE2-expressing cells. J. Biol. Chem. 281:3198–203 [Google Scholar]
  138. Glowacka I, Bertram S, Muller MA, Allen P, Soilleux E. 138.  et al. 2011. Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response. J. Virol. 85:4122–34 [Google Scholar]
  139. Bertram S, Glowacka I, Muller MA, Lavender H, Gnirss K. 139.  et al. 2011. Cleavage and activation of the severe acute respiratory syndrome coronavirus spike protein by human airway trypsin-like protease. J. Virol. 85:13363–72 [Google Scholar]
  140. Shulla A, Heald-Sargent T, Subramanya G, Zhao J, Perlman S, Gallagher T. 140.  2011. A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry. J. Virol. 85:873–82 [Google Scholar]
  141. Matsuyama S, Ujike M, Morikawa S, Tashiro M, Taguchi F. 141.  2005. Protease-mediated enhancement of severe acute respiratory syndrome coronavirus infection. PNAS 102:12543–47 [Google Scholar]
  142. Kam YW, Okumura Y, Kido H, Ng LF, Bruzzone R, Altmeyer R. 142.  2009. Cleavage of the SARS coronavirus spike glycoprotein by airway proteases enhances virus entry into human bronchial epithelial cells in vitro. PLOS ONE 4:e7870 [Google Scholar]
  143. Belouzard S, Chu VC, Whittaker GR. 143.  2009. Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites. PNAS 106:5871–76 [Google Scholar]
  144. Belouzard S, Madu I, Whittaker GR. 144.  2010. Elastase-mediated activation of the severe acute respiratory syndrome coronavirus spike protein at discrete sites within the S2 domain. J. Biol. Chem. 285:22758–63 [Google Scholar]
  145. Beniac DR, deVarennes SL, Andonov A, He R, Booth TF. 145.  2007. Conformational reorganization of the SARS coronavirus spike following receptor binding: implications for membrane fusion. PLOS ONE 2:e1082 [Google Scholar]
  146. Simmons G, Zmora P, Gierer S, Heurich A, Pohlmann S. 146.  2013. Proteolytic activation of the SARS-coronavirus spike protein: cutting enzymes at the cutting edge of antiviral research. Antivir. Res. 100:605–14 [Google Scholar]
  147. Millet JK, Whittaker GR. 147.  2014. Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein. PNAS 111:15214–19 [Google Scholar]
  148. Qian Z, Dominguez SR, Holmes KV. 148.  2013. Role of the spike glycoprotein of human Middle East respiratory syndrome coronavirus (MERS-CoV) in virus entry and syncytia formation. PLOS ONE 8:e76469 [Google Scholar]
  149. Shirato K, Kawase M, Matsuyama S. 149.  2013. Middle East respiratory syndrome coronavirus infection mediated by the transmembrane serine protease TMPRSS2. J. Virol. 87:12552–61 [Google Scholar]
  150. Gierer S, Bertram S, Kaup F, Wrensch F, Heurich A. 150.  et al. 2014. The spike protein of the emerging β-coronavirus EMC uses a novel coronavirus receptor for entry, can be activated by TMPRSS2, and is targeted by neutralizing antibodies. J. Virol. 87:5502–11 [Google Scholar]
  151. Gierer S, Muller MA, Heurich A, Ritz D, Springstein BL. 151.  et al. 2015. Inhibition of proprotein convertases abrogates processing of the Middle Eastern respiratory syndrome coronavirus spike protein in infected cells but does not reduce viral infectivity. J. Infect. Dis. 211:889–97 [Google Scholar]
  152. Yang Y, Liu C, Du L, Jiang S, Shi Z. 152.  et al. 2015. Two mutations were critical for bat-to-human transmission of Middle East respiratory syndrome coronavirus. J. Virol. 89:9119–23 [Google Scholar]
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