1932

Abstract

Ebola virus (EBOV) emerged in West Africa in 2014 to devastating effect, and demonstrated that infection can cause a broad range of severe disease manifestations. As the virus itself was genetically similar to other Zaire ebolaviruses, the spectrum of pathology likely resulted from variable responses to infection in a large and genetically diverse population. This review comprehensively summarizes current knowledge of the host response to EBOV infection, including pathways hijacked by the virus to facilitate replication, host processes that contribute directly to pathogenesis, and host-pathogen interactions involved in subverting or antagonizing host antiviral immunity.

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2016-08-31
2024-06-19
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Literature Cited

  1. Adu-Gyamfi E, Johnson KA, Fraser ME, Scott JL, Soni SP. 1.  et al. 2015. Host cell plasma membrane phosphatidylserine regulates the assembly and budding of Ebola virus. J. Virol. 89:9440–53 [Google Scholar]
  2. Adu-Gyamfi E, Soni SP, Xue Y, Digman MA, Gratton E, Stahelin RV. 2.  2013. The Ebola virus matrix protein penetrates into the plasma membrane: a key step in viral protein 40 (VP40) oligomerization and viral egress. J. Biol. Chem. 288:5779–89 [Google Scholar]
  3. Aleksandrowicz P, Marzi A, Biedenkopf N, Beimforde N, Becker S. 3.  et al. 2011. Ebola virus enters host cells by macropinocytosis and clathrin-mediated endocytosis. J. Infect. Dis. 204:Suppl. 3S957–67 [Google Scholar]
  4. Azarian T, Lo Presti A, Giovanetti M, Cella E, Rife B. 4.  et al. 2015. Impact of spatial dispersion, evolution, and selection on Ebola Zaire Virus epidemic waves. Sci. Rep. 5:10170 [Google Scholar]
  5. Bah EI, Lamah MC, Fletcher T, Jacob ST, Brett-Major DM. 5.  et al. 2015. Clinical presentation of patients with Ebola virus disease in Conakry, Guinea. N. Engl. J. Med. 372:40–47 [Google Scholar]
  6. Bale S, Julien JP, Bornholdt ZA, Krois AS, Wilson IA, Saphire EO. 6.  2013. Ebolavirus VP35 coats the backbone of double-stranded RNA for interferon antagonism. J. Virol. 87:10385–88 [Google Scholar]
  7. Basler CF, Mikulasova A, Martinez-Sobrido L, Paragas J, Muhlberger E. 7.  et al. 2003. The Ebola virus VP35 protein inhibits activation of interferon regulatory factor 3. J. Virol. 77:7945–56 [Google Scholar]
  8. Bhattacharyya S, Hope TJ, Young JA. 8.  2011. Differential requirements for clathrin endocytic pathway components in cellular entry by Ebola and Marburg glycoprotein pseudovirions. Virology 419:1–9 [Google Scholar]
  9. Bhattacharyya S, Warfield KL, Ruthel G, Bavari S, Aman MJ, Hope TJ. 9.  2010. Ebola virus uses clathrin-mediated endocytosis as an entry pathway. Virology 401:18–28 [Google Scholar]
  10. Biedenkopf N, Hartlieb B, Hoenen T, Becker S. 10.  2013. Phosphorylation of Ebola virus VP30 influences the composition of the viral nucleocapsid complex: impact on viral transcription and replication. J. Biol. Chem. 288:11165–74 [Google Scholar]
  11. Bradfute SB, Swanson PE, Smith MA, Watanabe E, McDunn JE. 11.  et al. 2010. Mechanisms and consequences of ebolavirus-induced lymphocyte apoptosis. J. Immunol. 184:327–35 [Google Scholar]
  12. Bradfute SB, Warfield KL, Bavari S. 12.  2008. Functional CD8+ T cell responses in lethal Ebola virus infection. J. Immunol. 180:4058–66 [Google Scholar]
  13. Brecher M, Schornberg KL, Delos SE, Fusco ML, Saphire EO, White JM. 13.  2012. Cathepsin cleavage potentiates the Ebola virus glycoprotein to undergo a subsequent fusion-relevant conformational change. J. Virol. 86:364–72 [Google Scholar]
  14. Brindley MA, Hunt CL, Kondratowicz AS, Bowman J, Sinn PL. 14.  et al. 2011. Tyrosine kinase receptor Axl enhances entry of Zaire ebolavirus without direct interactions with the viral glycoprotein. Virology 415:83–94 [Google Scholar]
  15. Brudner M, Karpel M, Lear C, Chen L, Yantosca LM. 15.  et al. 2013. Lectin-dependent enhancement of Ebola virus infection via soluble and transmembrane C-type lectin receptors. PLOS ONE 8:e60838 [Google Scholar]
  16. Cardenas WB, Loo YM, Gale M Jr., Hartman AL, Kimberlin CR. 16.  et al. 2006. Ebola virus VP35 protein binds double-stranded RNA and inhibits alpha/beta interferon production induced by RIG-I signaling. J. Virol. 80:5168–78 [Google Scholar]
  17. Carette JE, Raaben M, Wong AC, Herbert AS, Obernosterer G. 17.  et al. 2011. Ebola virus entry requires the cholesterol transporter Niemann-Pick C1. Nature 477:340–43 [Google Scholar]
  18. Chandran K, Sullivan NJ, Felbor U, Whelan SP, Cunningham JM. 18.  2005. Endosomal proteolysis of the Ebola virus glycoprotein is necessary for infection. Science 308:1643–45 [Google Scholar]
  19. Chang TH, Kubota T, Matsuoka M, Jones S, Bradfute SB. 19.  et al. 2009. Ebola Zaire virus blocks type I interferon production by exploiting the host SUMO modification machinery. PLOS Pathog. 5:e1000493 [Google Scholar]
  20. Chertow DS, Kleine C, Edwards JK, Scaini R, Giuliani R, Sprecher A. 20.  2014. Ebola virus disease in West Africa—clinical manifestations and management. N. Engl. J. Med. 371:2054–57 [Google Scholar]
  21. Cilloniz C, Ebihara H, Ni C, Neumann G, Korth MJ. 21.  et al. 2011. Functional genomics reveals the induction of inflammatory response and metalloproteinase gene expression during lethal Ebola virus infection. J. Virol. 85:9060–68 [Google Scholar]
  22. Connolly BM, Steele KE, Davis KJ, Geisbert TW, Kell WM. 22.  et al. 1999. Pathogenesis of experimental Ebola virus infection in guinea pigs. J. Infect. Dis. 179:Suppl. 1S203–17 [Google Scholar]
  23. Cote M, Misasi J, Ren T, Bruchez A, Lee K. 23.  et al. 2011. Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus infection. Nature 477:344–48 [Google Scholar]
  24. Cross RW, Fenton KA, Geisbert JB, Mire CE, Geisbert TW. 24.  2015. Modeling the disease course of Zaire ebolavirus infection in the outbred guinea pig. J. Infect. Dis. 212:Suppl. 2S305–15 [Google Scholar]
  25. Dallatomasina S, Crestani R, Sylvester Squire J, Declerk H, Caleo GM. 25.  et al. 2015. Ebola outbreak in rural West Africa: epidemiology, clinical features and outcomes. Trop. Med. Int. Health 20:448–54 [Google Scholar]
  26. de La Vega MA, Caleo G, Audet J, Qiu X, Kozak RA. 26.  et al. 2015. Ebola viral load at diagnosis associates with patient outcome and outbreak evolution. J. Clin. Investig. 125:4421–28 [Google Scholar]
  27. Ebihara H, Rockx B, Marzi A, Feldmann F, Haddock E. 27.  et al. 2011. Host response dynamics following lethal infection of rhesus macaques with Zaire ebolavirus. J. Infect. Dis. 204:Suppl. 3S991–99 [Google Scholar]
  28. Ebihara H, Zivcec M, Gardner D, Falzarano D, LaCasse R. 28.  et al. 2013. A Syrian golden hamster model recapitulating Ebola hemorrhagic fever. J. Infect. Dis. 207:306–18 [Google Scholar]
  29. Empig CJ, Goldsmith MA. 29.  2002. Association of the caveola vesicular system with cellular entry by filoviruses. J. Virol. 76:5266–70 [Google Scholar]
  30. Escudero-Perez B, Volchkova VA, Dolnik O, Lawrence P, Volchkov VE. 30.  2014. Shed GP of Ebola virus triggers immune activation and increased vascular permeability. PLOS Pathog. 10:e1004509 [Google Scholar]
  31. Fisher-Hoch SP, Brammer TL, Trappier SG, Hutwagner LC, Farrar BB. 31.  et al. 1992. Pathogenic potential of filoviruses: role of geographic origin of primate host and virus strain. J. Infect. Dis. 166:753–63 [Google Scholar]
  32. Francica JR, Varela-Rohena A, Medvec A, Plesa G, Riley JL, Bates P. 32.  2010. Steric shielding of surface epitopes and impaired immune recognition induced by the Ebola virus glycoprotein. PLOS Pathog. 6:e1001098 [Google Scholar]
  33. Gabriel G, Feldmann F, Reimer R, Thiele S, Fischer M. 33.  et al. 2015. Importin-α7 is involved in the formation of Ebola virus inclusion bodies but is not essential for pathogenicity in mice. J. Infect. Dis. 212:Suppl. 2S316–21 [Google Scholar]
  34. Garcia-Dorival I, Wu W, Dowall S, Armstrong S, Touzelet O. 34.  et al. 2014. Elucidation of the Ebola virus VP24 cellular interactome and disruption of virus biology through targeted inhibition of host-cell protein function. J. Proteome Res. 13:5120–35 [Google Scholar]
  35. Geisbert TW, Hensley LE, Jahrling PB, Larsen T, Geisbert JB. 35.  et al. 2003. Treatment of Ebola virus infection with a recombinant inhibitor of factor VIIa/tissue factor: a study in rhesus monkeys. Lancet 362:1953–58 [Google Scholar]
  36. Geisbert TW, Hensley LE, Larsen T, Young HA, Reed DS. 36.  et al. 2003. Pathogenesis of Ebola hemorrhagic fever in cynomolgus macaques: evidence that dendritic cells are early and sustained targets of infection. Am. J. Pathol. 163:2347–70 [Google Scholar]
  37. Geisbert TW, Young HA, Jahrling PB, Davis KJ, Kagan E, Hensley LE. 37.  2003. Mechanisms underlying coagulation abnormalities in Ebola hemorrhagic fever: overexpression of tissue factor in primate monocytes/macrophages is a key event. J. Infect. Dis. 188:1618–29 [Google Scholar]
  38. Geisbert TW, Young HA, Jahrling PB, Davis KJ, Larsen T. 38.  et al. 2003. Pathogenesis of Ebola hemorrhagic fever in primate models: evidence that hemorrhage is not a direct effect of virus-induced cytolysis of endothelial cells. Am. J. Pathol. 163:2371–82 [Google Scholar]
  39. Gibb TR, Bray M, Geisbert TW, Steele KE, Kell WM. 39.  et al. 2001. Pathogenesis of experimental Ebola Zaire virus infection in BALB/c mice. J. Comp. Pathol. 125:233–42 [Google Scholar]
  40. Hacke M, Bjorkholm P, Hellwig A, Himmels P, de Almodovar CR. 40.  et al. 2015. Inhibition of Ebola virus glycoprotein-mediated cytotoxicity by targeting its transmembrane domain and cholesterol. Nat. Commun. 6:7688 [Google Scholar]
  41. Halfmann P, Neumann G, Kawaoka Y. 41.  2011. The Ebolavirus VP24 protein blocks phosphorylation of p38 mitogen-activated protein kinase. J. Infect. Dis. 204:Suppl. 3S953–56 [Google Scholar]
  42. Han Z, Madara JJ, Liu Y, Liu W, Ruthel G. 42.  et al. 2015. ALIX rescues budding of a double PTAP/PPEY L-domain deletion mutant of Ebola VP40: a role for ALIX in Ebola virus egress. J. Infect. Dis. 212:Suppl. 2S138–45 [Google Scholar]
  43. Hartman AL, Bird BH, Towner JS, Antoniadou ZA, Zaki SR, Nichol ST. 43.  2008. Inhibition of IRF-3 activation by VP35 is critical for the high level of virulence of Ebola virus. J. Virol. 82:2699–704 [Google Scholar]
  44. Hensley LE, Stevens EL, Yan SB, Geisbert JB, Macias WL. 44.  et al. 2007. Recombinant human activated protein C for the postexposure treatment of Ebola hemorrhagic fever. J. Infect. Dis. 196:Suppl. 2S390–99 [Google Scholar]
  45. Hensley LE, Young HA, Jahrling PB, Geisbert TW. 45.  2002. Proinflammatory response during Ebola virus infection of primate models: possible involvement of the tumor necrosis factor receptor superfamily. Immunol. Lett. 80:169–79 [Google Scholar]
  46. Hoenen T, Safronetz D, Groseth A, Wollenberg KR, Koita OA. 46.  et al. 2015. Mutation rate and genotype variation of Ebola virus from Mali case sequences. Science 348:117–19 [Google Scholar]
  47. Hoenen T, Shabman RS, Groseth A, Herwig A, Weber M. 47.  et al. 2012. Inclusion bodies are a site of ebolavirus replication. J. Virol. 86:11779–88 [Google Scholar]
  48. Huang IC, Bailey CC, Weyer JL, Radoshitzky SR, Becker MM. 48.  et al. 2011. Distinct patterns of IFITM-mediated restriction of filoviruses, SARS coronavirus, and influenza A virus. PLOS Pathog. 7:e1001258 [Google Scholar]
  49. Hunt CL, Kolokoltsov AA, Davey RA, Maury W. 49.  2011. The Tyro3 receptor kinase Axl enhances macropinocytosis of Zaire ebolavirus. J. Virol. 85:334–47 [Google Scholar]
  50. Ilinykh PA, Lubaki NM, Widen SG, Renn LA, Theisen TC. 50.  et al. 2015. Different temporal effects of Ebola virus VP35 and VP24 proteins on global gene expression in human dendritic cells. J. Virol. 89:7567–83 [Google Scholar]
  51. Ilinykh PA, Tigabu B, Ivanov A, Ammosova T, Obukhov Y. 51.  et al. 2014. Role of protein phosphatase 1 in dephosphorylation of Ebola virus VP30 protein and its targeting for the inhibition of viral transcription. J. Biol. Chem. 289:22723–38 [Google Scholar]
  52. Kaletsky RL, Simmons G, Bates P. 52.  2007. Proteolysis of the Ebola virus glycoproteins enhances virus binding and infectivity. J. Virol. 81:13378–84 [Google Scholar]
  53. Kash JC, Muhlberger E, Carter V, Grosch M, Perwitasari O. 53.  et al. 2006. Global suppression of the host antiviral response by Ebola- and Marburgviruses: increased antagonism of the type I interferon response is associated with enhanced virulence. J. Virol. 80:3009–20 [Google Scholar]
  54. Kimberlin CR, Bornholdt ZA, Li S, Woods VL Jr., MacRae IJ, Saphire EO. 54.  2010. Ebolavirus VP35 uses a bimodal strategy to bind dsRNA for innate immune suppression. PNAS 107:314–19 [Google Scholar]
  55. Kindrachuk J, Wahl-Jensen V, Safronetz D, Trost B, Hoenen T. 55.  et al. 2014. Ebola virus modulates transforming growth factor β signaling and cellular markers of mesenchyme-like transition in hepatocytes. J. Virol. 88:9877–92 [Google Scholar]
  56. Kubota T, Matsuoka M, Chang TH, Bray M, Jones S. 56.  et al. 2009. Ebolavirus VP35 interacts with the cytoplasmic dynein light chain 8. J. Virol. 83:6952–56 [Google Scholar]
  57. Kucharski AJ, Edmunds WJ. 57.  2014. Case fatality rate for Ebola virus disease in west Africa. Lancet 384:1260 [Google Scholar]
  58. Kuroda M, Fujikura D, Nanbo A, Marzi A, Noyori O. 58.  et al. 2015. Interaction between TIM-1 and NPC1 is important for cellular entry of Ebola virus. J. Virol. 89:6481–93 [Google Scholar]
  59. Lado M, Walker NF, Baker P, Haroon S, Brown CS. 59.  et al. 2015. Clinical features of patients isolated for suspected Ebola virus disease at Connaught Hospital, Freetown, Sierra Leone: a retrospective cohort study. Lancet Infect. Dis. 15:1024–33 [Google Scholar]
  60. Lanini S, Portella G, Vairo F, Kobinger GP, Pesenti A. 60.  et al. 2015. Blood kinetics of Ebola virus in survivors and nonsurvivors. J. Clin. Investig. 125:4692–98 [Google Scholar]
  61. Le Guenno B, Formenty P, Wyers M, Gounon P, Walker F, Boesch C. 61.  1995. Isolation and partial characterisation of a new strain of Ebola virus. Lancet 345:1271–74 [Google Scholar]
  62. Lennemann NJ, Rhein BA, Ndungo E, Chandran K, Qiu X, Maury W. 62.  2014. Comprehensive functional analysis of N-linked glycans on Ebola virus GP1. mBio 5:e00862–13 [Google Scholar]
  63. Leung DW, Ginder ND, Fulton DB, Nix J, Basler CF. 63.  et al. 2009. Structure of the Ebola VP35 interferon inhibitory domain. PNAS 106:411–16 [Google Scholar]
  64. Leung DW, Prins KC, Borek DM, Farahbakhsh M, Tufariello JM. 64.  et al. 2010. Structural basis for dsRNA recognition and interferon antagonism by Ebola VP35. Nat. Struct. Mol. Biol. 17:165–72 [Google Scholar]
  65. Leung LW, Martinez O, Reynard O, Volchkov VE, Basler CF. 65.  2011. Ebola virus failure to stimulate plasmacytoid dendritic cell interferon responses correlates with impaired cellular entry. J. Infect. Dis. 204:Suppl. 3S973–77 [Google Scholar]
  66. Licata JM, Simpson-Holley M, Wright NT, Han Z, Paragas J, Harty RN. 66.  2003. Overlapping motifs (PTAP and PPEY) within the Ebola virus VP40 protein function independently as late budding domains: involvement of host proteins TSG101 and VPS-4. J. Virol. 77:1812–19 [Google Scholar]
  67. Lin G, Simmons G, Pohlmann S, Baribaud F, Ni H. 67.  et al. 2003. Differential N-linked glycosylation of human immunodeficiency virus and Ebola virus envelope glycoproteins modulates interactions with DC-SIGN and DC-SIGNR. J. Virol. 77:1337–46 [Google Scholar]
  68. Lu HJ, Qian J, Kargbo D, Zhang XG, Yang F. 68.  et al. 2015. Ebola virus outbreak investigation, Sierra Leone, September 28–November 11, 2014. Emerg. Infect. Dis. 21:1921–27 [Google Scholar]
  69. Luthra P, Jordan DS, Leung DW, Amarasinghe GK, Basler CF. 69.  2015. Ebola virus VP35 interaction with dynein LC8 regulates viral RNA synthesis. J. Virol. 89:5148–53 [Google Scholar]
  70. Martinez MJ, Volchkova VA, Raoul H, Alazard-Dany N, Reynard O, Volchkov VE. 70.  2011. Role of VP30 phosphorylation in the Ebola virus replication cycle. J. Infect. Dis. 204:Suppl. 3S934–40 [Google Scholar]
  71. Martinez O, Johnson JC, Honko A, Yen B, Shabman RS. 71.  et al. 2013. Ebola virus exploits a monocyte differentiation program to promote its entry. J. Virol. 87:3801–14 [Google Scholar]
  72. Martinez O, Ndungo E, Tantral L, Miller EH, Leung LW. 72.  et al. 2013. A mutation in the Ebola virus envelope glycoprotein restricts viral entry in a host species- and cell-type-specific manner. J. Virol. 87:3324–34 [Google Scholar]
  73. Martins K, Cooper C, Warren T, Wells J, Bell T. 73.  et al. 2015. Characterization of clinical and immunological parameters during Ebola virus infection of rhesus macaques. Viral Immunol. 28:32–41 [Google Scholar]
  74. Marzi A, Akhavan A, Simmons G, Gramberg T, Hofmann H. 74.  et al. 2006. The signal peptide of the ebolavirus glycoprotein influences interaction with the cellular lectins DC-SIGN and DC-SIGNR. J. Virol. 80:6305–17 [Google Scholar]
  75. Marzi A, Moller P, Hanna SL, Harrer T, Eisemann J. 75.  et al. 2007. Analysis of the interaction of Ebola virus glycoprotein with DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin) and its homologue DC-SIGNR. J. Infect. Dis. 196:Suppl. 2S237–46 [Google Scholar]
  76. Mateo M, Carbonnelle C, Reynard O, Kolesnikova L, Nemirov K. 76.  et al. 2011. VP24 is a molecular determinant of Ebola virus virulence in guinea pigs. J. Infect. Dis. 204:Suppl. 3S1011–20 [Google Scholar]
  77. Mateo M, Reid SP, Leung LW, Basler CF, Volchkov VE. 77.  2010. Ebolavirus VP24 binding to karyopherins is required for inhibition of interferon signaling. J. Virol. 84:1169–75 [Google Scholar]
  78. Matsuno K, Nakayama E, Noyori O, Marzi A, Ebihara H. 78.  et al. 2010. C-type lectins do not act as functional receptors for filovirus entry into cells. Biochem. Biophys. Res. Commun. 403:144–48 [Google Scholar]
  79. McElroy AK, Akondy RS, Davis CW, Ellebedy AH, Mehta AK. 79.  et al. 2015. Human Ebola virus infection results in substantial immune activation. PNAS 112:4719–24 [Google Scholar]
  80. Mingo RM, Simmons JA, Shoemaker CJ, Nelson EA, Schornberg KL. 80.  et al. 2015. Ebola virus and severe acute respiratory syndrome coronavirus display late cell entry kinetics: evidence that transport to NPC1+ endolysosomes is a rate-defining step. J. Virol. 89:2931–43 [Google Scholar]
  81. Misasi J, Chandran K, Yang JY, Considine B, Filone CM. 81.  et al. 2012. Filoviruses require endosomal cysteine proteases for entry but exhibit distinct protease preferences. J. Virol. 86:3284–92 [Google Scholar]
  82. Modrof J, Muhlberger E, Klenk HD, Becker S. 82.  2002. Phosphorylation of VP30 impairs Ebola virus transcription. J. Biol. Chem. 277:33099–104 [Google Scholar]
  83. Mohamadzadeh M, Coberley SS, Olinger GG, Kalina WV, Ruthel G. 83.  et al. 2006. Activation of triggering receptor expressed on myeloid cells-1 on human neutrophils by Marburg and Ebola viruses. J. Virol. 80:7235–44 [Google Scholar]
  84. Mohan GS, Li W, Ye L, Compans RW, Yang C. 84.  2012. Antigenic subversion: a novel mechanism of host immune evasion by Ebola virus. PLOS Pathog. 8:e1003065 [Google Scholar]
  85. Nanbo A, Imai M, Watanabe S, Noda T, Takahashi K. 85.  et al. 2010. Ebolavirus is internalized into host cells via macropinocytosis in a viral glycoprotein-dependent manner. PLOS Pathog. 6:e1001121 [Google Scholar]
  86. Nanbo A, Watanabe S, Halfmann P, Kawaoka Y. 86.  2013. The spatio-temporal distribution dynamics of Ebola virus proteins and RNA in infected cells. Sci. Rep. 3:1206 [Google Scholar]
  87. Neumann G, Watanabe S, Kawaoka Y. 87.  2009. Characterization of Ebolavirus regulatory genomic regions. Virus Res. 144:1–7 [Google Scholar]
  88. Noda T, Kolesnikova L, Becker S, Kawaoka Y. 88.  2011. The importance of the NP: VP35 ratio in Ebola virus nucleocapsid formation. J. Infect. Dis. 204:Suppl. 3S878–83 [Google Scholar]
  89. O'Hearn A, Wang M, Cheng H, Lear-Rooney CM, Koning K. 89.  et al. 2015. Role of EXT1 and glycosaminoglycans in the early stage of filovirus entry. J. Virol. 89:5441–49 [Google Scholar]
  90. Okumura A, Pitha PM, Harty RN. 90.  2008. ISG15 inhibits Ebola VP40 VLP budding in an L-domain-dependent manner by blocking Nedd4 ligase activity. PNAS 105:3974–79 [Google Scholar]
  91. Okumura A, Pitha PM, Yoshimura A, Harty RN. 91.  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]
  92. Okumura A, Rasmussen AL, Halfmann P, Feldmann F, Yoshimura A. 92.  et al. 2015. Suppressor of cytokine signaling 3 is an inducible host factor that regulates virus egress during Ebola virus infection. J. Virol. 89:10399–406 [Google Scholar]
  93. Olabode AS, Jiang X, Robertson DL, Lovell SC. 93.  2015. Ebolavirus is evolving but not changing: no evidence for functional change in EBOV from 1976 to the 2014 outbreak. Virology 482:202–7 [Google Scholar]
  94. Park DJ, Dudas G, Wohl S, Goba A, Whitmer SL. 94.  et al. 2015. Ebola virus epidemiology, transmission, and evolution during seven months in Sierra Leone. Cell 161:1516–26 [Google Scholar]
  95. Perry DL, Bollinger L, White GL. 95.  2012. The baboon (Papio spp.) as a model of human Ebola virus infection. Viruses 4:2400–16 [Google Scholar]
  96. Prins KC, Cardenas WB, Basler CF. 96.  2009. Ebola virus protein VP35 impairs the function of interferon regulatory factor-activating kinases IKKε and TBK-1. J. Virol. 83:3069–77 [Google Scholar]
  97. Prins KC, Delpeut S, Leung DW, Reynard O, Volchkova VA. 97.  et al. 2010. Mutations abrogating VP35 interaction with double-stranded RNA render Ebola virus avirulent in guinea pigs. J. Virol. 84:3004–15 [Google Scholar]
  98. Qin E, Bi J, Zhao M, Wang Y, Guo T. 98.  et al. 2015. Clinical features of patients with Ebola virus disease in Sierra Leone. Clin. Infect. Dis. 61:491–95 [Google Scholar]
  99. Quinn K, Brindley MA, Weller ML, Kaludov N, Kondratowicz A. 99.  et al. 2009. Rho GTPases modulate entry of Ebola virus and vesicular stomatitis virus pseudotyped vectors. J. Virol. 83:10176–86 [Google Scholar]
  100. Rasmussen AL, Okumura A, Ferris MT, Green R, Feldmann F. 100.  et al. 2014. Host genetic diversity enables Ebola hemorrhagic fever pathogenesis and resistance. Science 346:987–91 [Google Scholar]
  101. Reed DS, Hensley LE, Geisbert JB, Jahrling PB, Geisbert TW. 101.  2004. Depletion of peripheral blood T lymphocytes and NK cells during the course of Ebola hemorrhagic fever in cynomolgus macaques. Viral Immunol. 17:390–400 [Google Scholar]
  102. Reid SP, Leung LW, Hartman AL, Martinez O, Shaw ML. 102.  et al. 2006. Ebola virus VP24 binds karyopherin α1 and blocks STAT1 nuclear accumulation. J. Virol. 80:5156–67 [Google Scholar]
  103. Reid SP, Valmas C, Martinez O, Sanchez FM, Basler CF. 103.  2007. Ebola virus VP24 proteins inhibit the interaction of NPI-1 subfamily karyopherin α proteins with activated STAT1. J. Virol. 81:13469–77 [Google Scholar]
  104. Rubins KH, Hensley LE, Wahl-Jensen V, Daddario DiCaprio KM, Young HA. 104.  et al. 2007. The temporal program of peripheral blood gene expression in the response of nonhuman primates to Ebola hemorrhagic fever. Genome Biol. 8:R174 [Google Scholar]
  105. Ryabchikova EI, Kolesnikova LV, Luchko SV. 105.  1999. An analysis of features of pathogenesis in two animal models of Ebola virus infection. J. Infect. Dis. 179:Suppl. 1S199–202 [Google Scholar]
  106. Saeed MF, Kolokoltsov AA, Albrecht T, Davey RA. 106.  2010. Cellular entry of Ebola virus involves uptake by a macropinocytosis-like mechanism and subsequent trafficking through early and late endosomes. PLOS Pathog. 6:e1001110 [Google Scholar]
  107. Saeed MF, Kolokoltsov AA, Freiberg AN, Holbrook MR, Davey RA. 107.  2008. Phosphoinositide-3 kinase-Akt pathway controls cellular entry of Ebola virus. PLOS Pathog. 4:e1000141 [Google Scholar]
  108. Sakurai Y, Kolokoltsov AA, Chen CC, Tidwell MW, Bauta WE. 108.  et al. 2015. Two-pore channels control Ebola virus host cell entry and are drug targets for disease treatment. Science 347:995–98 [Google Scholar]
  109. Salvador B, Sexton NR, Carrion R Jr., Nunneley J, Patterson JL. 109.  et al. 2013. Filoviruses utilize glycosaminoglycans for their attachment to target cells. J. Virol. 87:3295–304 [Google Scholar]
  110. Sanchez A, Geisbert TW, Feldmann H. 110.  2007. Filoviridae: Marburg and Ebola viruses. Fields Virology 1 DM Knipe, PM Howley 1409–48 Philadelphia: Lippincott Williams & Wilkins, 5th ed.. [Google Scholar]
  111. Sanchez A, Lukwiya M, Bausch D, Mahanty S, Sanchez AJ. 111.  et al. 2004. Analysis of human peripheral blood samples from fatal and nonfatal cases of Ebola (Sudan) hemorrhagic fever: cellular responses, virus load, and nitric oxide levels. J. Virol. 78:10370–77 [Google Scholar]
  112. Schieffelin JS, Shaffer JG, Goba A, Gbakie M, Gire SK. 112.  et al. 2014. Clinical illness and outcomes in patients with Ebola in Sierra Leone. N. Engl. J. Med. 371:2092–100 [Google Scholar]
  113. Schornberg KL, Matsuyama S, Kabsch K, Delos S, Bouton A, White J. 113.  2006. Role of endosomal cathepsins in entry mediated by the Ebola virus glycoprotein. J. Virol. 80:4174–78 [Google Scholar]
  114. Schornberg KL, Shoemaker CJ, Dube D, Abshire MY, Delos SE. 114.  et al. 2009. α5β1-Integrin controls ebolavirus entry by regulating endosomal cathepsins. PNAS 106:8003–8 [Google Scholar]
  115. Schudt G, Dolnik O, Kolesnikova L, Biedenkopf N, Herwig A, Becker S. 115.  2015. Transport of ebolavirus nucleocapsids is dependent on actin polymerization: live-cell imaging analysis of ebolavirus-infected cells. J. Infect. Dis. 212:Suppl. 2S160–66 [Google Scholar]
  116. Schumann M, Gantke T, Muhlberger E. 116.  2009. Ebola virus VP35 antagonizes PKR activity through its C-terminal interferon inhibitory domain. J. Virol. 83:8993–97 [Google Scholar]
  117. Shabman RS, Gulcicek EE, Stone KL, Basler CF. 117.  2011. The Ebola virus VP24 protein prevents hnRNP C1/C2 binding to karyopherin α1 and partially alters its nuclear import. J. Infect. Dis. 204:Suppl. 3S904–10 [Google Scholar]
  118. Shabman RS, Hoenen T, Groseth A, Jabado O, Binning JM. 118.  et al. 2013. An upstream open reading frame modulates ebola virus polymerase translation and virus replication. PLOS Pathog. 9:e1003147 [Google Scholar]
  119. Shabman RS, Leung DW, Johnson J, Glennon N, Gulcicek EE. 119.  et al. 2011. DRBP76 associates with Ebola virus VP35 and suppresses viral polymerase function. J. Infect. Dis. 204:Suppl. 3S911–18 [Google Scholar]
  120. Shimojima M, Ikeda Y, Kawaoka Y. 120.  2007. The mechanism of Axl-mediated Ebola virus infection. J. Infect. Dis. 196:Suppl. 2S259–63 [Google Scholar]
  121. Shimojima M, Takada A, Ebihara H, Neumann G, Fujioka K. 121.  et al. 2006. Tyro3 family-mediated cell entry of Ebola and Marburg viruses. J. Virol. 80:10109–16 [Google Scholar]
  122. Simmons G, Reeves JD, Grogan CC, Vandenberghe LH, Baribaud F. 122.  et al. 2003. DC-SIGN and DC-SIGNR bind Ebola glycoproteins and enhance infection of macrophages and endothelial cells. Virology 305:115–23 [Google Scholar]
  123. Simmons G, Rennekamp AJ, Chai N, Vandenberghe LH, Riley JL, Bates P. 123.  2003. Folate receptor alpha and caveolae are not required for Ebola virus glycoprotein-mediated viral infection. J. Virol. 77:13433–38 [Google Scholar]
  124. Soni SP, Adu-Gyamfi E, Yong SS, Jee CS, Stahelin RV. 124.  2013. The Ebola virus matrix protein deeply penetrates the plasma membrane: an important step in viral egress. Biophys. J. 104:1940–49 [Google Scholar]
  125. Soni SP, Stahelin RV. 125.  2014. The Ebola virus matrix protein VP40 selectively induces vesiculation from phosphatidylserine-enriched membranes. J. Biol. Chem. 289:33590–97 [Google Scholar]
  126. Strong JE, Wong G, Jones SE, Grolla A, Theriault S. 126.  et al. 2008. Stimulation of Ebola virus production from persistent infection through activation of the Ras/MAPK pathway. PNAS 105:17982–87 [Google Scholar]
  127. Takada A, Fujioka K, Tsuiji M, Morikawa A, Higashi N. 127.  et al. 2004. Human macrophage C-type lectin specific for galactose and N-acetylgalactosamine promotes filovirus entry. J. Virol. 78:2943–47 [Google Scholar]
  128. Takada A, Watanabe S, Ito H, Okazaki K, Kida H, Kawaoka Y. 128.  2000. Downregulation of β1 integrins by Ebola virus glycoprotein: implication for virus entry. Virology 278:20–26 [Google Scholar]
  129. Takahashi K, Halfmann P, Oyama M, Kozuka-Hata H, Noda T, Kawaoka Y. 129.  2013. DNA topoisomerase 1 facilitates the transcription and replication of the Ebola virus genome. J. Virol. 87:8862–69 [Google Scholar]
  130. Timmins J, Schoehn G, Ricard-Blum S, Scianimanico S, Vernet T. 130.  et al. 2003. Ebola virus matrix protein VP40 interaction with human cellular factors Tsg101 and Nedd4. J. Mol. Biol. 326:493–502 [Google Scholar]
  131. Tong YG, Shi WF, Liu D, Qian J, Liang L. 131.  et al. 2015. Genetic diversity and evolutionary dynamics of Ebola virus in Sierra Leone. Nature 524:93–96 [Google Scholar]
  132. Usami K, Matsuno K, Igarashi M, Denda-Nagai K, Takada A, Irimura T. 132.  2011. Involvement of viral envelope GP2 in Ebola virus entry into cells expressing the macrophage galactose-type C-type lectin. Biochem. Biophys. Res. Commun. 407:74–78 [Google Scholar]
  133. Wahl-Jensen V, Afanasieva TA, Seebach J, Stroher U, Feldmann H, Schnittler HJ. 133.  2005. Effects of Ebola virus glycoproteins on endothelial cell activation and barrier function. J. Virol. 79:10442–50 [Google Scholar]
  134. Wahl-Jensen V, Kurz SK, Feldmann F, Buehler LK, Kindrachuk J. 134.  et al. 2011. Ebola virion attachment and entry into human macrophages profoundly effects early cellular gene expression. PLOS Negl. Trop. Dis. 5:e1359 [Google Scholar]
  135. Wahl-Jensen V, Kurz SK, Hazelton PR, Schnittler HJ, Stroher U. 135.  et al. 2005. Role of Ebola virus secreted glycoproteins and virus-like particles in activation of human macrophages. J. Virol. 79:2413–19 [Google Scholar]
  136. Wauquier N, Becquart P, Padilla C, Baize S, Leroy EM. 136.  2010. Human fatal Zaire Ebola virus infection is associated with an aberrant innate immunity and with massive lymphocyte apoptosis. PLOS Negl. Trop. Dis. 4:e837 [Google Scholar]
  137. 137. WHO Ebola Response Team 2014. Ebola virus disease in West Africa—the first 9 months of the epidemic and forward projections. N. Engl. J. Med. 371:1481–95 [Google Scholar]
  138. Wong AC, Sandesara RG, Mulherkar N, Whelan SP, Chandran K. 138.  2010. A forward genetic strategy reveals destabilizing mutations in the ebolavirus glycoprotein that alter its protease dependence during cell entry. J. Virol. 84:163–75 [Google Scholar]
  139. Xu W, Edwards MR, Borek DM, Feagins AR, Mittal A. 139.  et al. 2014. Ebola virus VP24 targets a unique NLS binding site on karyopherin alpha 5 to selectively compete with nuclear import of phosphorylated STAT1. Cell Host Microbe 16:187–200 [Google Scholar]
  140. Yasuda J, Nakao M, Kawaoka Y, Shida H. 140.  2003. Nedd4 regulates egress of Ebola virus-like particles from host cells. J. Virol. 77:9987–92 [Google Scholar]
  141. Yen B, Mulder LC, Martinez O, Basler CF. 141.  2014. Molecular basis for ebolavirus VP35 suppression of human dendritic cell maturation. J. Virol. 88:12500–10 [Google Scholar]
  142. Yen JY, Garamszegi S, Geisbert JB, Rubins KH, Geisbert TW. 142.  et al. 2011. Therapeutics of Ebola hemorrhagic fever: whole-genome transcriptional analysis of successful disease mitigation. J. Infect. Dis. 204:Suppl. 3S1043–52 [Google Scholar]
  143. Yuan S, Cao L, Ling H, Dang M, Sun Y. 143.  et al. 2015. TIM-1 acts a dual-attachment receptor for Ebolavirus by interacting directly with viral GP and the PS on the viral envelope. Protein Cell 6:814–24 [Google Scholar]
  144. Zhang AP, Bornholdt ZA, Liu T, Abelson DM, Lee DE. 144.  et al. 2012. The Ebola virus interferon antagonist VP24 directly binds STAT1 and has a novel, pyramidal fold. PLOS Pathog. 8:e1002550 [Google Scholar]
  145. Zumbrun EE, Abdeltawab NF, Bloomfield HA, Chance TB, Nichols DK. 145.  et al. 2012. Development of a murine model for aerosolized ebolavirus infection using a panel of recombinant inbred mice. Viruses 4:3468–93 [Google Scholar]
  146. Zumbrun EE, Bloomfield HA, Dye JM, Hunter TC, Dabisch PA. 146.  et al. 2012. A characterization of aerosolized Sudan virus infection in African green monkeys, cynomolgus macaques, and rhesus macaques. Viruses 4:2115–36 [Google Scholar]
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