Virologica Sinica

, Volume 32, Issue 1, pp 3–15 | Cite as

The roles of ebolavirus glycoproteins in viral pathogenesis

  • Yun-Jia Ning
  • Fei Deng
  • Zhihong Hu
  • Hualin WangEmail author


Ebolaviruses are highly dangerous pathogens exhibiting extreme virulence in humans and nonhuman primates. The majority of ebolavirus species, most notably Zaire ebolavirus, can cause Ebola virus disease (EVD), formerly known as Ebola hemorrhagic fever, in humans. EVD is associated with case-fatality rates as high as 90%, and there is currently no specific treatment or licensed vaccine available against EVD. Understanding the molecular biology and pathogenesis of ebolaviruses is important for the development of antiviral therapeutics. Ebolavirus encodes several forms of glycoproteins (GPs), which have some interesting characteristics, including the transcriptional editing coding strategy and extensive O-glycosylation modification, clustered in the mucin-like domain of GP1, full-length GP (GP1,2), and shed GP. In addition to the canonical role of the spike protein, GP1,2, in viral entry, ebolavirus GPs appear to have multiple additional functions, likely contributing to the complex pathogenesis of the virus. Here, we review the roles of ebolavirus GPs in viral pathogenesis.


ebolavirus glycoprotein (GP) mucin-like domain (MLD) cytotoxicity immune evasion inflammation pathogenesis 



This work was supported by the National Natural Science Foundation of China (No. 31125003 and No. 31321001) and the Basic Work Program of the Ministry of Science and Technology of China (2013FY113500).

Compliance with Ethics Guidelines

The authors declare that they have no conflicts of interest. This article does not contain any studies with human or animal subjects performed by any of the authors.


  1. Ansari AA. 2014. Clinical features and pathobiology of Ebolavirus infection. J Autoimmun, 55: 1–9.Google Scholar
  2. Audet J, Kobinger GP. 2015. Immune evasion in ebolavirus infections. Viral Immunol, 28: 10–18.Google Scholar
  3. Baize S, Leroy EM, Georges-Courbot MC, Capron M, Lansoud-Soukate J, Debre P, Fisher-Hoch SP, McCormick JB, Georges AJ. 1999. Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in Ebola virusinfected patients. Nat Med, 5: 423–426.Google Scholar
  4. Baize S, Leroy EM, Georges AJ, Georges-Courbot MC, Capron M, Bedjabaga I, Lansoud-Soukate J, Mavoungou E. 2002. Inflammatory responses in Ebola virus-infected patients. Clin Exp Immunol, 128: 163–168.PubMedCentralPubMedGoogle Scholar
  5. Barrientos LG, Martin AM, Rollin PE, Sanchez A. 2004. Disulfide bond assignment of the Ebola virus secreted glycoprotein SGP. Biochem Biophys Res Commun, 323: 696–702.Google Scholar
  6. Basler CF. 2015. Innate immune evasion by filoviruses. Virology, 479–480: 122–130.Google Scholar
  7. Becker Y. 1995. Retrovirus and filovirus “immunosuppressive motif” and the evolution of virus pathogenicity in HIV-1, HIV-2, and Ebola viruses. Virus Genes, 11: 191–195.Google Scholar
  8. Bornholdt ZA, Turner HL, Murin CD, Li W, Sok D, Souders CA, Piper AE, Goff A, Shamblin JD, Wollen SE, Sprague TR, Fusco ML, Pommert KB, Cavacini LA, Smith HL, Klempner M, Reimann KA, Krauland E, Gerngross TU, Wittrup KD, Saphire EO, Burton DR, Glass PJ, Ward AB, Walker LM. 2016. Isolation of potent neutralizing antibodies from a survivor of the 2014 Ebola virus outbreak. Science, 351: 1078–1083.PubMedCentralPubMedGoogle Scholar
  9. Borrow P, Martinez-Sobrido L, de la Torre JC. 2010. Inhibition of the type I interferon antiviral response during arenavirus infection. Viruses, 2: 2443–2480.PubMedCentralPubMedGoogle Scholar
  10. Bosio CM, Moore BD, Warfield KL, Ruthel G, Mohamadzadeh M, Aman MJ, Bavari S. 2004. Ebola and Marburg virus-like particles activate human myeloid dendritic cells. Virology, 326: 280–287.Google Scholar
  11. Bray M, Geisbert TW. 2005. Ebola virus: the role of macrophages and dendritic cells in the pathogenesis of Ebola hemorrhagic fever. Int J Biochem Cell Biol, 37: 1560–1566.Google Scholar
  12. Bukreyev AA, Chandran K, Dolnik O, Dye JM, Ebihara H, Leroy EM, Muhlberger E, Netesov SV, Patterson JL, Paweska JT, Saphire EO, Smither SJ, Takada A, Towner JS, Volchkov VE, Warren TK, Kuhn JH. 2014. Discussions and decisions of the 2012–2014 International Committee on Taxonomy of Viruses (ICTV) Filoviridae Study Group, January 2012-June 2013. Arch Virol, 159: 821–830.PubMedCentralPubMedGoogle Scholar
  13. Chan SY, Ma MC, Goldsmith MA. 2000. Differential induction of cellular detachment by envelope glycoproteins of Marburg and Ebola (Zaire) viruses. J Gen Virol, 81: 2155–2159.Google Scholar
  14. Chertow DS, Kleine C, Edwards JK, Scaini R, Giuliani R, Sprecher A. 2014. Ebola virus disease in West Africa—clinical manifestations and management. N Engl J Med, 371: 2054–2057.Google Scholar
  15. Cilloniz C, Ebihara H, Ni C, Neumann G, Korth MJ, Kelly SM, Kawaoka Y, Feldmann H, Katze MG. 2011. Functional genomics reveals the induction of inflammatory response and metalloproteinase gene expression during lethal Ebola virus infection. J Virol, 85: 9060–9068.PubMedCentralPubMedGoogle Scholar
  16. Cook JD, Lee JE. 2013. The secret life of viral entry glycoproteins: moonlighting in immune evasion. PLoS Pathog, 9: e1003258.PubMedCentralPubMedGoogle Scholar
  17. Corti D, Misasi J, Mulangu S, Stanley DA, Kanekiyo M, Wollen S, Ploquin A, Doria-Rose NA, Staupe RP, Bailey M, Shi W, Choe M, Marcus H, Thompson EA, Cagigi A, Silacci C, Fernandez-Rodriguez B, Perez L, Sallusto F, Vanzetta F, Agatic G, Cameroni E, Kisalu N, Gordon I, Ledgerwood JE, Mascola JR, Graham BS, Muyembe-Tamfun JJ, Trefry JC, Lanzavecchia A, Sullivan NJ. 2016. Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody. Science, 351: 1339–1342.Google Scholar
  18. de La Vega MA, Wong G, Kobinger GP, Qiu X. 2015. The multiple roles of sGP in Ebola pathogenesis. Viral Immunol, 28: 3–9.Google Scholar
  19. Dias JM, Kuehne AI, Abelson DM, Bale S, Wong AC, Halfmann P, Muhammad MA, Fusco ML, Zak SE, Kang E, Kawaoka Y, Chandran K, Dye JM, Saphire EO. 2011. A shared structural solution for neutralizing ebolaviruses. Nat Struct Mol Biol, 18: 1424–1427.PubMedCentralPubMedGoogle Scholar
  20. Dolnik O, Volchkova V, Garten W, Carbonnelle C, Becker S, Kahnt R, Stroher U, Klenk HD, Volchkov V. 2004. Ectodomain shedding of the glycoprotein GP of Ebola virus. Embo Journal, 23: 2175–2184.Google Scholar
  21. Dolnik O, Volchkova VA, Escudero-Perez B, Lawrence P, Klenk HD, Volchkov VE. 2015. Shedding of Ebola Virus Surface Glycoprotein Is a Mechanism of Self-regulation of Cellular Cytotoxicity and Has a Direct Effect on Virus Infectivity. J Infect Dis, 212 Suppl 2: S322–328.Google Scholar
  22. Elliott RM, Weber F. 2009. Bunyaviruses and the type I interferon system. Viruses, 1: 1003–1021.PubMedCentralPubMedGoogle Scholar
  23. Errett JS, Gale M. 2015. Emerging complexity and new roles for the RIG-I-like receptors in innate antiviral immunity. Virol Sin, 30: 163–173.Google Scholar
  24. Escudero-Perez B, Volchkova VA, Dolnik O, Lawrence P, Volchkov VE. 2014. Shed GP of Ebola virus triggers immune activation and increased vascular permeability. PLoS Pathog, 10: e1004509.PubMedCentralPubMedGoogle Scholar
  25. Falzarano D, Feldmann H. 2015. Virology. Delineating Ebola entry. Science, 347: 947–948.Google Scholar
  26. Falzarano D, Krokhin O, Wahl-Jensen V, Seebach J, Wolf K, Schnittler HJ, Feldmann H. 2006. Structure-function analysis of the soluble glycoprotein, sGP, of Ebola virus. Chembiochem, 7: 1605–1611.Google Scholar
  27. Feldmann H, Geisbert TW. 2011. Ebola haemorrhagic fever. Lancet, 377: 849–862.PubMedCentralPubMedGoogle Scholar
  28. Fitzpatrick K, Skasko M, Deerinck TJ, Crum J, Ellisman MH, Guatelli J. 2010. Direct restriction of virus release and incorporation of the interferon-induced protein BST-2 into HIV-1 particles. PLoS Pathog, 6: e1000701.PubMedCentralPubMedGoogle Scholar
  29. Francica JR, Matukonis MK, Bates P. 2009. Requirements for cell rounding and surface protein down-regulation by Ebola virus glycoprotein. Virology, 383: 237–247.Google Scholar
  30. Francica JR, Varela-Rohena A, Medvec A, Plesa G, Riley JL, Bates P. 2010. Steric shielding of surface epitopes and impaired immune recognition induced by the ebola virus glycoprotein. PLoS Pathog, 6: e1001098.PubMedCentralPubMedGoogle Scholar
  31. Furuyama W, Marzi A, Nanbo A, Haddock E, Maruyama J, Miyamoto H, Igarashi M, Yoshida R, Noyori O, Feldmann H, Takada A. 2016. Discovery of an antibody for pan-ebolavirus therapy. Sci Rep, 6: 20514.PubMedCentralPubMedGoogle Scholar
  32. Gallaher WR, Garry RF. 2015. Modeling of the Ebola virus delta peptide reveals a potential lytic sequence motif. Viruses, 7: 285–305.PubMedCentralPubMedGoogle Scholar
  33. Geisbert TW, Hensley LE, Gibb TR, Steele KE, Jaax NK, Jahrling PB. 2000. Apoptosis induced in vitro and in vivo during infection by Ebola and Marburg viruses. Lab Invest, 80: 171–186.Google Scholar
  34. Geisbert TW, Hensley LE, Larsen T, Young HA, Reed DS, Geisbert JB, Scott DP, Kagan E, Jahrling PB, Davis KJ. 2003. Pathogenesis of Ebola hemorrhagic fever in cynomolgus macaques: evidence that dendritic cells are early and sustained targets of infection. Am J Pathol, 163: 2347–2370.PubMedCentralPubMedGoogle Scholar
  35. Gong X, Qian H, Zhou X, Wu J, Wan T, Cao P, Huang W, Zhao X, Wang X, Wang P, Shi Y, Gao GF, Zhou Q, Yan N. 2016. Structural Insights into the Niemann-Pick C1 (NPC1)-Mediated Cholesterol Transfer and Ebola Infection. Cell, 165: 1467–1478.Google Scholar
  36. Groseth A, Marzi A, Hoenen T, Herwig A, Gardner D, Becker S, Ebihara H, Feldmann H. 2012. The Ebola virus glycoprotein contributes to but is not sufficient for virulence in vivo. PLoS Pathog, 8: e1002847.PubMedCentralPubMedGoogle Scholar
  37. Gustin JK, Bai Y, Moses AV, Douglas JL. 2015. Ebola Virus Glycoprotein Promotes Enhanced Viral Egress by Preventing Ebola VP40 From Associating With the Host Restriction Factor BST2/Tetherin. J Infect Dis, 212 Suppl 2: S181–S190.PubMedCentralPubMedGoogle Scholar
  38. Hammonds J, Wang JJ, Yi H, Spearman P. 2010. Immunoelectron microscopic evidence for Tetherin/BST2 as the physical bridge between HIV-1 virions and the plasma membrane. PLoS Pathog, 6: e1000749.PubMedCentralPubMedGoogle Scholar
  39. Han Z, Boshra H, Sunyer JO, Zwiers SH, Paragas J, Harty RN. 2003. Biochemical and functional characterization of the Ebola virus VP24 protein: implications for a role in virus assembly and budding. J Virol, 77: 1793–1800.PubMedCentralPubMedGoogle Scholar
  40. Harty RN, Brown ME, Wang G, Huibregtse J, Hayes FP. 2000. A PPxY motif within the VP40 protein of Ebola virus interacts physically and functionally with a ubiquitin ligase: implications for filovirus budding. Proc Natl Acad Sci U S A, 97: 13871–13876.PubMedCentralPubMedGoogle Scholar
  41. Hinz A, Miguet N, Natrajan G, Usami Y, Yamanaka H, Renesto P, Hartlieb B, McCarthy AA, Simorre JP, Gottlinger H, Weissenhorn W. 2010. Structural basis of HIV-1 tethering to membranes by the BST-2/tetherin ectodomain. Cell Host Microbe, 7: 314–323.PubMedCentralPubMedGoogle Scholar
  42. Howell KA, Qiu X, Brannan JM, Bryan C, Davidson E, Holtsberg FW, Wec AZ, Shulenin S, Biggins JE, Douglas R, Enterlein SG, Turner HL, Pallesen J, Murin CD, He S, Kroeker A, Vu H, Herbert AS, Fusco ML, Nyakatura EK, Lai JR, Keck ZY, Foung SK, Saphire EO, Zeitlin L, Ward AB, Chandran K, Doranz BJ, Kobinger GP, Dye JM, Aman MJ. 2016. Antibody Treatment of Ebola and Sudan Virus Infection via a Uniquely Exposed Epitope within the Glycoprotein Receptor-Binding Site. Cell Rep, 15: 1514–1526.PubMedCentralPubMedGoogle Scholar
  43. Ito H, Watanabe S, Takada A, Kawaoka Y. 2001. Ebola virus glycoprotein: proteolytic processing, acylation, cell tropism, and detection of neutralizing antibodies. J Virol, 75: 1576–1580.PubMedCentralPubMedGoogle Scholar
  44. Iwasa A, Shimojima M, Kawaoka Y. 2011. sGP serves as a structural protein in Ebola virus infection. J Infect Dis, 204 Suppl 3: S897–S903.PubMedCentralPubMedGoogle Scholar
  45. Jeffers SA, Sanders DA, Sanchez A. 2002. Covalent modifications of the ebola virus glycoprotein. J Virol, 76: 12463–12472.PubMedCentralPubMedGoogle Scholar
  46. Jiang H, Wang J, Manicassamy B, Manicassamy S, Caffrey M, Rong L. 2009. The Role of the Charged Residues of the GP2 Helical Regions in Ebola Entry. Virol Sin, 24: 121–135.PubMedCentralPubMedGoogle Scholar
  47. Jouvenet N, Neil SJ, Zhadina M, Zang T, Kratovac Z, Lee Y, McNatt M, Hatziioannou T, Bieniasz PD. 2009. Broad-spectrum inhibition of retroviral and filoviral particle release by tetherin. J Virol, 83: 1837–1844.Google Scholar
  48. Kaletsky RL, Francica JR, Agrawal-Gamse C, Bates P. 2009. Tetherin-mediated restriction of filovirus budding is antagonized by the Ebola glycoprotein. Proc Natl Acad Sci U S A, 106: 2886–2891.PubMedCentralPubMedGoogle Scholar
  49. Kindzelskii AL, Yang Z, Nabel GJ, Todd RF, 3rd, Petty HR. 2000. Ebola virus secretory glycoprotein (sGP) diminishes Fc gamma RB-to-CR3 proximity on neutrophils. J Immunol, 164: 953–958.Google Scholar
  50. Kortepeter MG, Bausch DG, Bray M. 2011. Basic clinical and laboratory features of filoviral hemorrhagic fever. J Infect Dis, 204 Suppl 3: S810–S816.Google Scholar
  51. Kuhl A, Banning C, Marzi A, Votteler J, Steffen I, Bertram S, Glowacka I, Konrad A, Sturzl M, Guo JT, Schubert U, Feldmann H, Behrens G, Schindler M, Pohlmann S. 2011. The Ebola virus glycoprotein and HIV-1 Vpu employ different strategies to counteract the antiviral factor tetherin. J Infect Dis, 204 Suppl 3: S850–S860.PubMedCentralPubMedGoogle Scholar
  52. Kupzig S, Korolchuk V, Rollason R, Sugden A, Wilde A, Banting G. 2003. Bst-2/HM1.24 is a raft-associated apical membrane protein with an unusual topology. Traffic, 4: 694–709.Google Scholar
  53. Le Tortorec A, Willey S, Neil SJ. 2011. Antiviral inhibition of enveloped virus release by tetherin/BST-2: action and counteraction. Viruses, 3: 520–540.PubMedCentralPubMedGoogle Scholar
  54. Lee JE, Fusco ML, Hessell AJ, Oswald WB, Burton DR, Saphire EO. 2008. Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor. Nature, 454: 177–182.PubMedCentralPubMedGoogle Scholar
  55. Lee JE, Saphire EO. 2009. Ebolavirus glycoprotein structure and mechanism of entry. Future Virol, 4: 621–635.PubMedCentralPubMedGoogle Scholar
  56. Lennemann NJ, Rhein BA, Ndungo E, Chandran K, Qiu X, Maury W. 2014. Comprehensive functional analysis of N-linked glycans on Ebola virus GP1. MBio, 5: e00862–00813.PubMedCentralPubMedGoogle Scholar
  57. Lopez LA, Yang SJ, Exline CM, Rengarajan S, Haworth KG, Cannon PM. 2012. Anti-tetherin activities of HIV-1 Vpu and Ebola virus glycoprotein do not involve removal of tetherin from lipid rafts. J Virol, 86: 5467–5480.PubMedCentralPubMedGoogle Scholar
  58. Lopez LA, Yang SJ, Hauser H, Exline CM, Haworth KG, Oldenburg J, Cannon PM. 2010. Ebola virus glycoprotein counteracts BST-2/Tetherin restriction in a sequence-independent manner that does not require tetherin surface removal. J Virol, 84: 7243–7255.PubMedCentralPubMedGoogle Scholar
  59. Ma DY, Suthar MS. 2015. Mechanisms of innate immune evasion in re-emerging RNA viruses. Curr Opin Virol, 12: 26–37.PubMedCentralPubMedGoogle Scholar
  60. Mahanty S, Bray M. 2004. Pathogenesis of filoviral haemorrhagic fevers. Lancet Infect Dis, 4: 487–498.Google Scholar
  61. Martines RB, Ng DL, Greer PW, Rollin PE, Zaki SR. 2015. Tissue and cellular tropism, pathology and pathogenesis of Ebola and Marburg viruses. J Pathol, 235: 153–174.Google Scholar
  62. Martinez O, Tantral L, Mulherkar N, Chandran K, Basler CF. 2011. Impact of Ebola mucin-like domain on antiglycoprotein antibody responses induced by Ebola virus-like particles. J Infect Dis, 204 Suppl 3: S825–S832.PubMedCentralPubMedGoogle Scholar
  63. Martinez O, Valmas C, Basler CF. 2007. Ebola virus-like particleinduced activation of NF-kappaB and Erk signaling in human dendritic cells requires the glycoprotein mucin domain. Virology, 364: 342–354.PubMedCentralPubMedGoogle Scholar
  64. Mehedi M, Falzarano D, Seebach J, Hu X, Carpenter MS, Schnittler HJ, Feldmann H. 2011. A new Ebola virus nonstructural glycoprotein expressed through RNA editing. J Virol, 85: 5406–5414.PubMedCentralPubMedGoogle Scholar
  65. Messaoudi I, Amarasinghe GK, Basler CF. 2015. Filovirus patho-genesis and immune evasion: insights from Ebola virus and Marburg virus. Nat Rev Microbiol, 13: 663–676.PubMedCentralPubMedGoogle Scholar
  66. Misasi J, Gilman MS, Kanekiyo M, Gui M, Cagigi A, Mulangu S, Corti D, Ledgerwood JE, Lanzavecchia A, Cunningham J, Muyembe-Tamfun JJ, Baxa U, Graham BS, Xiang Y, Sullivan NJ, McLellan JS. 2016. Structural and molecular basis for Ebola virus neutralization by protective human antibodies. Science, 351: 1343–1346.PubMedCentralPubMedGoogle Scholar
  67. Mohan GS, Li W, Ye L, Compans RW, Yang C. 2012. Antigenic subversion: a novel mechanism of host immune evasion by Ebola virus. PLoS Pathog, 8: e1003065.PubMedCentralPubMedGoogle Scholar
  68. Mohan GS, Ye L, Li W, Monteiro A, Lin X, Sapkota B, Pollack BP, Compans RW, Yang C. 2015. Less is more: Ebola virus surface glycoprotein expression levels regulate virus production and infectivity. J Virol, 89: 1205–1217.Google Scholar
  69. Moller-Tank S, Maury W. 2015. Ebola virus entry: a curious and complex series of events. PLoS Pathog, 11: e1004731.PubMedCentralPubMedGoogle Scholar
  70. Nakayama E, Saijo M. 2013. Animal models for Ebola and Marburg virus infections. Front Microbiol, 4: 267.PubMedCentralPubMedGoogle Scholar
  71. Ning YJ, Feng K, Min YQ, Cao WC, Wang M, Deng F, Hu Z, Wang H. 2015. Disruption of type I interferon signaling by the nonstructural protein of severe fever with thrombocytopenia syndrome virus via the hijacking of STAT2 and STAT1 into inclusion bodies. J Virol, 89: 4227–4236.PubMedCentralPubMedGoogle Scholar
  72. Ning YJ, Wang M, Deng M, Shen S, Liu W, Cao WC, Deng F, Wang YY, Hu Z, Wang H. 2014. Viral suppression of innate immunity via spatial isolation of TBK1/IKKepsilon from mitochondrial antiviral platform. J Mol Cell Biol, 6: 324–337.Google Scholar
  73. Okumura A, Pitha PM, Yoshimura A, Harty RN. 2010. Interaction between Ebola virus glycoprotein and host toll-like receptor 4 leads to induction of proinflammatory cytokines and SOCS1. J Virol, 84: 27–33.Google Scholar
  74. Pallesen J, Murin CD, de Val N, Cottrell CA, Hastie KM, Turner HL, Fusco ML, Flyak AI, Zeitlin L, Crowe JE, Jr., Andersen KG, Saphire EO, Ward AB. 2016. Structures of Ebola virus GP and sGP in complex with therapeutic antibodies. Nat Microbiol, 1: 16128.PubMedCentralPubMedGoogle Scholar
  75. Panchal RG, Ruthel G, Kenny TA, Kallstrom GH, Lane D, Badie SS, Li L, Bavari S, Aman MJ. 2003. In vivo oligomerization and raft localization of Ebola virus protein VP40 during vesicular budding. Proc Natl Acad Sci U S A, 100: 15936–15941.PubMedCentralPubMedGoogle Scholar
  76. Perez-Caballero D, Zang T, Ebrahimi A, McNatt MW, Gregory DA, Johnson MC, Bieniasz PD. 2009. Tetherin inhibits HIV-1 release by directly tethering virions to cells. Cell, 139: 499–511.PubMedCentralPubMedGoogle Scholar
  77. Peters CJ, LeDuc JW. 1999. An introduction to Ebola: the virus and the disease. J Infect Dis, 179 Suppl 1: ix–xvi.Google Scholar
  78. Qiu X, Wong G, Audet J, Bello A, Fernando L, Alimonti JB, Fausther-Bovendo H, Wei H, Aviles J, Hiatt E, Johnson A, Morton J, Swope K, Bohorov O, Bohorova N, Goodman C, Kim D, Pauly MH, Velasco J, Pettitt J, Olinger GG, Whaley K, Xu B, Strong JE, Zeitlin L, Kobinger GP. 2014. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature, 514: 47–53.PubMedCentralPubMedGoogle Scholar
  79. Radoshitzky SR, Warfield KL, Chi X, Dong L, Kota K, Bradfute SB, Gearhart JD, Retterer C, Kranzusch PJ, Misasi JN, Hogenbirk MA, Wahl-Jensen V, Volchkov VE, Cunningham JM, Jahrling PB, Aman MJ, Bavari S, Farzan M, Kuhn JH. 2011. Ebolavirus delta-peptide immunoadhesins inhibit marburgvirus and ebolavirus cell entry. J Virol, 85: 8502–8513.PubMedCentralPubMedGoogle Scholar
  80. Randall RE, Goodbourn S. 2008. Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J Gen Virol, 89: 1–47.Google Scholar
  81. Reynard O, Borowiak M, Volchkova VA, Delpeut S, Mateo M, Volchkov VE. 2009. Ebolavirus glycoprotein GP masks both its own epitopes and the presence of cellular surface proteins. J Virol, 83: 9596–9601.PubMedCentralPubMedGoogle Scholar
  82. Ritchie G, Harvey DJ, Stroeher U, Feldmann F, Feldmann H, Wahl-Jensen V, Royle L, Dwek RA, Rudd PM. 2010. Identification of N-glycans from Ebola virus glycoproteins by matrixassisted laser desorption/ionisation time-of-flight and negative ion electrospray tandem mass spectrometry. Rapid Commun Mass Spectrom, 24: 571–585.PubMedCentralPubMedGoogle Scholar
  83. Rougeron V, Feldmann H, Grard G, Becker S, Leroy EM. 2015. Ebola and Marburg haemorrhagic fever. J Clin Virol, 64: 111–119.Google Scholar
  84. Sadler AJ, Williams BR. 2008. Interferon-inducible antiviral effectors. Nat Rev Immunol, 8: 559–568.PubMedCentralPubMedGoogle Scholar
  85. Sanchez A, Trappier SG, Mahy BW, Peters CJ, Nichol ST. 1996. The virion glycoproteins of Ebola viruses are encoded in two reading frames and are expressed through transcriptional editing. Proc Natl Acad Sci U S A, 93: 3602–3607.PubMedCentralPubMedGoogle Scholar
  86. Sanchez A, Yang ZY, Xu L, Nabel GJ, Crews T, Peters CJ. 1998. Biochemical analysis of the secreted and virion glycoproteins of Ebola virus. J Virol, 72: 6442–6447.PubMedCentralPubMedGoogle Scholar
  87. Sanchez AJ, Vincent MJ, Erickson BR, Nichol ST. 2006. Crimeancongo hemorrhagic fever virus glycoprotein precursor is cleaved by Furin-like and SKI-1 proteases to generate a novel 38-kilodalton glycoprotein. Journal of Virology, 80: 514–525.PubMedCentralPubMedGoogle Scholar
  88. Schneider WM, Chevillotte MD, Rice CM. 2014. Interferon-stimulated genes: a complex web of host defenses. Annu Rev Immunol, 32: 513–545.PubMedCentralPubMedGoogle Scholar
  89. Schnittler HJ, Feldmann H. 1998. Marburg and Ebola hemorrhagic fevers: does the primary course of infection depend on the accessibility of organ-specific macrophages? Clin Infect Dis, 27: 404–406.Google Scholar
  90. Shurtleff AC, Bavari S. 2015. Animal models for ebolavirus countermeasures discovery: what defines a useful model? Expert Opin Drug Discov, 10: 685–702.Google Scholar
  91. Simmons G, Wool-Lewis RJ, Baribaud F, Netter RC, Bates P. 2002. Ebola virus glycoproteins induce global surface protein down-modulation and loss of cell adherence. J Virol, 76: 2518–2528.PubMedCentralPubMedGoogle Scholar
  92. Singh G, Kumar A, Singh K, Kaur J. 2015. Ebola virus: an introduction and its pathology. Rev Med Virol. doi: 10.1002/rmv.1863.Google Scholar
  93. Stark GR. 2007. How cells respond to interferons revisited: from early history to current complexity. Cytokine Growth Factor Rev, 18: 419–423.PubMedCentralPubMedGoogle Scholar
  94. Sui J, Marasco WA. 2002. Evidence against Ebola virus sGP binding to human neutrophils by a specific receptor. Virology, 303: 9–14.Google Scholar
  95. Takada A. 2012. Filovirus tropism: cellular molecules for viral entry. Front Microbiol, 3: 34.PubMedCentralPubMedGoogle Scholar
  96. Takada A, Watanabe S, Ito H, Okazaki K, Kida H, Kawaoka Y. 2000. Downregulation of beta1 integrins by Ebola virus glycoprotein: implication for virus entry. Virology, 278: 20–26.Google Scholar
  97. Tang H. 2016. Uncovering the mystery of Ebola virus entry: Lock and key. Sci China Life Sci, 59: 434–435.Google Scholar
  98. To KK, Chan JF, Tsang AK, Cheng VC, Yuen KY. 2015. Ebola virus disease: a highly fatal infectious disease reemerging in West Africa. Microbes Infect, 17: 84–97.Google Scholar
  99. Tokarev A, Skasko M, Fitzpatrick K, Guatelli J. 2009. Antiviral activity of the interferon-induced cellular protein BST-2/tetherin. AIDS Res Hum Retroviruses, 25: 1197–1210.PubMedCentralPubMedGoogle Scholar
  100. U.S. Centers for Disease Control and Prevention. 2016a. 2014 Ebola outbreak in West Africa-case counts. Available: Accessed: April 14, 2016.Google Scholar
  101. U.S. Centers for Disease Control and Prevention. 2016b. Cost of the Ebola epidemic. Available: Accessed: May 3, 2016.Google Scholar
  102. Van Damme N, Goff D, Katsura C, Jorgenson RL, Mitchell R, Johnson MC, Stephens EB, Guatelli J. 2008. The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated from the cell surface by the viral Vpu protein. Cell Host Microbe, 3: 245–252.PubMedCentralPubMedGoogle Scholar
  103. Vande Burgt NH, Kaletsky RL, Bates P. 2015. Requirements within the Ebola Viral Glycoprotein for Tetherin Antagonism. Viruses, 7: 5587–5602.Google Scholar
  104. Volchkov VE. 1999. Processing of the Ebola virus glycoprotein. Curr Top Microbiol Immunol, 235: 35–47.Google Scholar
  105. Volchkov VE, Becker S, Volchkova VA, Ternovoj VA, Kotov AN, Netesov SV, Klenk HD. 1995. GP mRNA of Ebola virus is edited by the Ebola virus polymerase and by T7 and vaccinia virus polymerases. Virology, 214: 421–430.Google Scholar
  106. Volchkov VE, Blinov VM, Netesov SV. 1992. The envelope glycoprotein of Ebola virus contains an immunosuppressive-like domain similar to oncogenic retroviruses. FEBS Lett, 305: 181–184.Google Scholar
  107. Volchkov VE, Feldmann H, Volchkova VA, Klenk HD. 1998a. Processing of the Ebola virus glycoprotein by the proprotein convertase furin. Proc Natl Acad Sci U S A, 95: 5762–5767.PubMedCentralPubMedGoogle Scholar
  108. Volchkov VE, Volchkova VA, Muhlberger E, Kolesnikova LV, Weik M, Dolnik O, Klenk HD. 2001. Recovery of infectious Ebola virus from complementary DNA: RNA editing of the GP gene and viral cytotoxicity. Science, 291: 1965–1969.Google Scholar
  109. Volchkov VE, Volchkova VA, Slenczka W, Klenk HD, Feldmann H. 1998b. Release of viral glycoproteins during Ebola virus infection. Virology, 245: 110–119.Google Scholar
  110. Volchkova VA, Klenk HD, Volchkov VE. 1999. Delta-peptide is the carboxy-terminal cleavage fragment of the nonstructural small glycoprotein sGP of Ebola virus. Virology, 265: 164–171.Google Scholar
  111. Wahl-Jensen V, Kurz SK, Hazelton PR, Schnittler HJ, Stroher U, Burton DR, Feldmann H. 2005a. Role of Ebola virus secreted glycoproteins and virus-like particles in activation of human macrophages. J Virol, 79: 2413–2419.PubMedCentralPubMedGoogle Scholar
  112. Wahl-Jensen VM, Afanasieva TA, Seebach J, Stroher U, Feldmann H, Schnittler HJ. 2005b. Effects of Ebola virus glycoproteins on endothelial cell activation and barrier function. J Virol, 79: 10442–10450.PubMedCentralPubMedGoogle Scholar
  113. Wang H, Shi Y, Song J, Qi J, Lu G, Yan J, Gao GF. 2016. Ebola Viral Glycoprotein Bound to Its Endosomal Receptor Niemann-Pick C1. Cell, 164: 258–268.Google Scholar
  114. Wang J, Manicassamy B, Caffrey M, Rong L. 2011. Characterization of the receptor-binding domain of Ebola glycoprotein in viral entry. Virol Sin, 26: 156–170.Google Scholar
  115. Wec AZ, Nyakatura EK, Herbert AS, Howell KA, Holtsberg FW, Bakken RR, Mittler E, Christin JR, Shulenin S, Jangra RK, Bharrhan S, Kuehne AI, Bornholdt ZA, Flyak AI, Saphire EO, Crowe JE, Jr., Aman MJ, Dye JM, Lai JR, Chandran K. 2016. A “Trojan horse” bispecific antibody strategy for broad protection against ebolaviruses. Science. pii: aag3267.Google Scholar
  116. Wertheim JO, Worobey M. 2009. Relaxed selection and the evolution of RNA virus mucin-like pathogenicity factors. J Virol, 83: 4690–4694.PubMedCentralPubMedGoogle Scholar
  117. White JM, Whittaker GR. 2016. Fusion of Enveloped Viruses in Endosomes. Traffic, 17: 593–614.PubMedCentralPubMedGoogle Scholar
  118. Wilson JA, Hevey M, Bakken R, Guest S, Bray M, Schmaljohn AL, Hart MK. 2000. Epitopes involved in antibody-mediated protection from Ebola virus. Science, 287: 1664–1666.Google Scholar
  119. Wool-Lewis RJ, Bates P. 1999. Endoproteolytic processing of the ebola virus envelope glycoprotein: cleavage is not required for function. J Virol, 73: 1419–1426.PubMedCentralPubMedGoogle Scholar
  120. Yaddanapudi K, Palacios G, Towner JS, Chen I, Sariol CA, Nichol ST, Lipkin WI. 2006. Implication of a retrovirus-like glycoprotein peptide in the immunopathogenesis of Ebola and Marburg viruses. Faseb Journal, 20: 2519–2530.Google Scholar
  121. Yang ZY, Duckers HJ, Sullivan NJ, Sanchez A, Nabel EG, Nabel GJ. 2000. Identification of the Ebola virus glycoprotein as the main viral determinant of vascular cell cytotoxicity and injury. Nat Med, 6: 886–889.Google Scholar
  122. Ye J, Zhu B, Fu ZF, Chen H, Cao S. 2013. Immune evasion strategies of flaviviruses. Vaccine, 31: 461–471.Google Scholar
  123. Ye L, Lin JG, Sun YL, Bennouna S, Lo M, Wu QY, Bu ZG, Pulendran B, Compans RW, Yang CL. 2006. Ebola virus-like particles produced in insect cells exhibit dendritic cell stimulating activity and induce neutralizing antibodies. Virology, 351: 260–270.Google Scholar
  124. Zaki SR, Goldsmith CS. 1999. Pathologic features of filovirus infections in humans. Curr Top Microbiol Immunol, 235: 97–116.Google Scholar
  125. Zhao D, Han X, Zheng X, Wang H, Yang Z, Liu D, Han K, Liu J, Wang X, Yang W, Dong Q, Yang S, Xia X, Tang L, He F. 2016. The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein. PLoS Pathog, 12: e1005487.PubMedCentralPubMedGoogle Scholar

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Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors and Affiliations

  • Yun-Jia Ning
    • 1
  • Fei Deng
    • 1
  • Zhihong Hu
    • 1
  • Hualin Wang
    • 1
    Email author
  1. 1.State Key Laboratory of Virology, Wuhan Institute of VirologyChinese Academy of SciencesWuhanChina

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