Skip to main content

Host Factors Involved in Ebola Virus Replication

  • Chapter
  • First Online:
Roles of Host Gene and Non-coding RNA Expression in Virus Infection

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 419))

Abstract

Ebola virus (EBOV) is a highly pathogenic emerging virus that represents a serious threat to global public health and a major priority for biodefense. The 2014 West African outbreak demonstrated the potential of EBOV to cause an epidemic affecting thousands of people. The severity of disease and high case fatality rate of EBOV is largely due to the host response elicited by the virus. EBOV infection hijacks a number of host pathways to carry out replication and stimulate potent inflammatory responses, while simultaneously subverting the host antiviral immune response. Together, these events trigger a complex, systemic, often lethal febrile disease characterized by high levels of inflammatory cytokines, acute hepatitis and liver dysfunction, immune antagonism, gastrointestinal distress, and, in some cases, hemorrhage caused by coagulopathy and vascular leakage. This review presents current knowledge about the particular host responses induced and disrupted by EBOV infection and how these contribute to virus replication, immune evasion, pathogenesis, and disease outcome.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

References

  • Adu-Gyamfi E, Digman MA, Gratton E, Stahelin RV (2012) Single-particle tracking demonstrates that actin coordinates the movement of the Ebola virus matrix protein. Biophys J 103(9):L41–L43. doi:10.1016/j.bpj.2012.09.026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Adu-Gyamfi E, Soni SP, Xue Y, Digman MA, Gratton E, Stahelin RV (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(8):5779–5789. doi:10.1074/jbc.M112.443960

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Adu-Gyamfi E, Johnson KA, Fraser ME, Scott JL, Soni SP, Jones KR, Digman MA, Gratton E, Tessier CR, Stahelin RV (2015) Host Cell Plasma Membrane Phosphatidylserine Regulates the Assembly and Budding of Ebola Virus. J Virol 89(18):9440–9453. doi:10.1128/JVI.01087-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aleksandrowicz P, Marzi A, Biedenkopf N, Beimforde N, Becker S, Hoenen T, Feldmann H, Schnittler HJ (2011) Ebola virus enters host cells by macropinocytosis and clathrin-mediated endocytosis. J Infect Dis 204(Suppl 3):S957–S967. doi:10.1093/infdis/jir326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alvarez CP, Lasala F, Carrillo J, Muniz O, Corbi AL, Delgado R (2002) C-type lectins DC-SIGN and L-SIGN mediate cellular entry by Ebola virus in cis and in trans. J Virol 76(13):6841–6844

    Article  CAS  Google Scholar 

  • Arranz J, Lundeby KM, Hassan S, Zabala Fuentes LM, San Jose Garces P, Haaskjold YL, Bolkan HA, Krogh KO, Jongopi J, Mellesmo S, Josendal O, Opstad A, Svensen E, Kamara AS, Roberts DP, Stamper PD, Austin P, Moosa AJ, Marke D, Berg A, Blomberg B, Riera M (2016) Clinical features of suspected Ebola cases referred to the Moyamba ETC, Sierra Leone: challenges in the later stages of the 2014 outbreak. BMC Infect Dis 16:308. doi:10.1186/s12879-016-1609-9

    Article  PubMed  PubMed Central  Google Scholar 

  • Bah EI, Lamah MC, Fletcher T, Jacob ST, Brett-Major DM, Sall AA, Shindo N, Fischer WA 2nd, Lamontagne F, Saliou SM, Bausch DG, Moumie B, Jagatic T, Sprecher A, Lawler JV, Mayet T, Jacquerioz FA, Mendez Baggi MF, Vallenas C, Clement C, Mardel S, Faye O, Faye O, Soropogui B, Magassouba N, Koivogui L, Pinto R, Fowler RA (2015) Clinical presentation of patients with Ebola virus disease in Conakry, Guinea. The N Engl J Med 372(1):40–47. doi:10.1056/NEJMoa1411249

    Article  CAS  PubMed  Google Scholar 

  • 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 virus-infected patients. Nat Med 5(4):423–426. doi:10.1038/7422

    Article  CAS  PubMed  Google Scholar 

  • Baize S, Pannetier D, Oestereich L, Rieger T, Koivogui L, Magassouba N, Soropogui B, Sow MS, Keita S, De Clerck H, Tiffany A, Dominguez G, Loua M, Traore A, Kolie M, Malano ER, Heleze E, Bocquin A, Mely S, Raoul H, Caro V, Cadar D, Gabriel M, Pahlmann M, Tappe D, Schmidt-Chanasit J, Impouma B, Diallo AK, Formenty P, Van Herp M, Gunther S (2014) Emergence of Zaire Ebola virus disease in Guinea. The N Engl J Med 371(15):1418–1425. doi:10.1056/NEJMoa1404505

    Article  CAS  PubMed  Google Scholar 

  • Bale S, Liu T, Li S, Wang Y, Abelson D, Fusco M, Woods VL Jr, Saphire EO (2011) Ebola virus glycoprotein needs an additional trigger, beyond proteolytic priming for membrane fusion. PLoS neglected tropical diseases 5(11):e1395. doi:10.1371/journal.pntd.0001395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bale S, Julien JP, Bornholdt ZA, Krois AS, Wilson IA, Saphire EO (2013) Ebolavirus VP35 coats the backbone of double-stranded RNA for interferon antagonism. J Virol 87(18):10385–10388. doi:10.1128/JVI.01452-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Basharat Z, Yasmin A (2015) In silico assessment of phosphorylation and O-beta-GlcNAcylation sites in human NPC1 protein critical for Ebola virus entry. Infect Genet Evol 34:326–338. doi:10.1016/j.meegid.2015.06.001

    Article  CAS  PubMed  Google Scholar 

  • Basler CF, Mikulasova A, Martinez-Sobrido L, Paragas J, Muhlberger E, Bray M, Klenk HD, Palese P, Garcia-Sastre A (2003) The Ebola virus VP35 protein inhibits activation of interferon regulatory factor 3. J Virol 77(14):7945–7956

    Article  CAS  Google Scholar 

  • Beniac DR, Melito PL, Devarennes SL, Hiebert SL, Rabb MJ, Lamboo LL, Jones SM, Booth TF (2012) The organisation of Ebola virus reveals a capacity for extensive, modular polyploidy. PLoS ONE 7(1):e29608. doi:10.1371/journal.pone.0029608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bharat TA, Noda T, Riches JD, Kraehling V, Kolesnikova L, Becker S, Kawaoka Y, Briggs JA (2012) Structural dissection of Ebola virus and its assembly determinants using cryo-electron tomography. Proc Natl Acad Sci USA 109(11):4275–4280. doi:10.1073/pnas.1120453109

    Article  PubMed  Google Scholar 

  • Bhattacharyya S, Warfield KL, Ruthel G, Bavari S, Aman MJ, Hope TJ (2010) Ebola virus uses clathrin-mediated endocytosis as an entry pathway. Virology 401(1):18–28. doi:10.1016/j.virol.2010.02.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bhattacharyya S, Hope TJ, Young JA (2011) Differential requirements for clathrin endocytic pathway components in cellular entry by Ebola and Marburg glycoprotein pseudovirions. Virology 419(1):1–9. doi:10.1016/j.virol.2011.07.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bhattacharyya S, Zagorska A, Lew ED, Shrestha B, Rothlin CV, Naughton J, Diamond MS, Lemke G, Young JA (2013) Enveloped viruses disable innate immune responses in dendritic cells by direct activation of TAM receptors. Cell Host Microbe 14(2):136–147. doi:10.1016/j.chom.2013.07.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Biedenkopf N, Hartlieb B, Hoenen T, Becker S (2013) Phosphorylation of Ebola virus VP30 influences the composition of the viral nucleocapsid complex: impact on viral transcription and replication. J Biol Chem 288(16):11165–11174. doi:10.1074/jbc.M113.461285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Biedenkopf N, Lier C, Becker S (2016a) Dynamic Phosphorylation of VP30 Is Essential for Ebola Virus Life Cycle. J Virol 90(10):4914–4925. doi:10.1128/JVI.03257-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Biedenkopf N, Schlereth J, Grunweller A, Becker S, Hartmann RK (2016b) RNA binding of Ebola virus VP30 is essential for activating viral transcription. J Virol 90(16):7481–7496. doi:10.1128/JVI.00271-16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bird BH, Spengler JR, Chakrabarti AK, Khristova ML, Sealy TK, Coleman-McCray JD, Martin BE, Dodd KA, Goldsmith CS, Sanders J, Zaki SR, Nichol ST, Spiropoulou CF (2016) Humanized mouse model of ebola virus disease mimics the immune responses in human disease. J Infect Dis 213(5):703–711. doi:10.1093/infdis/jiv538

    Article  CAS  PubMed  Google Scholar 

  • Booth L, Roberts JL, Ecroyd H, Tritsch SR, Bavari S, Reid SP, Proniuk S, Zukiwski A, Jacob A, Sepulveda CS, Giovannoni F, Garcia CC, Damonte E, Gonzalez-Gallego J, Tunon MJ, Dent P (2016) AR-12 inhibits multiple chaperones concomitant with stimulating autophagosome formation collectively preventing virus replication. J Cell Physiol 231(10):2286–2302. doi:10.1002/jcp.25431

    Article  CAS  PubMed  Google Scholar 

  • Bornholdt ZA, Ndungo E, Fusco ML, Bale S, Flyak AI, Crowe JE Jr, Chandran K, Saphire EO (2016a) Host-primed ebola virus GP exposes a hydrophobic NPC1 receptor-binding pocket, revealing a target for broadly neutralizing antibodies. mBio 7(1):e02154–e02115. doi:10.1128/mBio.02154-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 (2016b) Isolation of potent neutralizing antibodies from a survivor of the 2014 Ebola virus outbreak. Science 351(6277):1078–1083. doi:10.1126/science.aad5788

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bradfute SB, Braun DR, Shamblin JD, Geisbert JB, Paragas J, Garrison A, Hensley LE, Geisbert TW (2007) Lymphocyte death in a mouse model of Ebola virus infection. J Infect Dis 196(Suppl 2):S296–S304. doi:10.1086/520602

    Article  PubMed  Google Scholar 

  • Bradfute SB, Warfield KL, Bavari S (2008) Functional CD8 + T cell responses in lethal Ebola virus infection. J Immunol 180(6):4058–4066

    Article  CAS  Google Scholar 

  • Bradfute SB, Swanson PE, Smith MA, Watanabe E, McDunn JE, Hotchkiss RS, Bavari S (2010) Mechanisms and consequences of ebolavirus-induced lymphocyte apoptosis. J Immunol 184(1):327–335. doi:10.4049/jimmunol.0901231

    Article  CAS  PubMed  Google Scholar 

  • Brecher M, Schornberg KL, Delos SE, Fusco ML, Saphire EO, White JM (2012) Cathepsin cleavage potentiates the Ebola virus glycoprotein to undergo a subsequent fusion-relevant conformational change. J Virol 86(1):364–372. doi:10.1128/JVI.05708-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brindley MA, Hunt CL, Kondratowicz AS, Bowman J, Sinn PL, McCray PB Jr, Quinn K, Weller ML, Chiorini JA, Maury W (2011) Tyrosine kinase receptor Axl enhances entry of Zaire ebolavirus without direct interactions with the viral glycoprotein. Virology 415(2):83–94. doi:10.1016/j.virol.2011.04.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brudner M, Karpel M, Lear C, Chen L, Yantosca LM, Scully C, Sarraju A, Sokolovska A, Zariffard MR, Eisen DP, Mungall BA, Kotton DN, Omari A, Huang IC, Farzan M, Takahashi K, Stuart L, Stahl GL, Ezekowitz AB, Spear GT, Olinger GG, Schmidt EV, Michelow IC (2013) Lectin-dependent enhancement of Ebola virus infection via soluble and transmembrane C-type lectin receptors. PLoS One 8(4):e60838. doi:10.1371/journal.pone.0060838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bwaka MA, Bonnet MJ, Calain P, Colebunders R, De Roo A, Guimard Y, Katwiki KR, Kibadi K, Kipasa MA, Kuvula KJ, Mapanda BB, Massamba M, Mupapa KD, Muyembe-Tamfum JJ, Ndaberey E, Peters CJ, Rollin PE, Van den Enden E, Van den Enden E (1999) Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo: clinical observations in 103 patients. J Infect Dis 179(Suppl 1):S1–S7. doi:10.1086/514308

    Article  PubMed  Google Scholar 

  • Caballero IS, Honko AN, Gire SK, Winnicki SM, Mele M, Gerhardinger C, Lin AE, Rinn JL, Sabeti PC, Hensley LE, Connor JH (2016) In vivo Ebola virus infection leads to a strong innate response in circulating immune cells. BMC Genom 17:707. doi:10.1186/s12864-016-3060-0

    Article  CAS  Google Scholar 

  • Cardenas WB, Loo YM, Gale M Jr, Hartman AL, Kimberlin CR, Martinez-Sobrido L, Saphire EO, Basler CF (2006) Ebola virus VP35 protein binds double-stranded RNA and inhibits alpha/beta interferon production induced by RIG-I signaling. J Virol 80(11):5168–5178. doi:10.1128/JVI.02199-05

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carette JE, Raaben M, Wong AC, Herbert AS, Obernosterer G, Mulherkar N, Kuehne AI, Kranzusch PJ, Griffin AM, Ruthel G, Dal Cin P, Dye JM, Whelan SP, Chandran K, Brummelkamp TR (2011) Ebola virus entry requires the cholesterol transporter Niemann-Pick C1. Nature 477(7364):340–343. doi:10.1038/nature10348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chandran K, Sullivan NJ, Felbor U, Whelan SP, Cunningham JM (2005) Endosomal proteolysis of the Ebola virus glycoprotein is necessary for infection. Science 308(5728):1643–1645. doi:10.1126/science.1110656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang TH, Kubota T, Matsuoka M, Jones S, Bradfute SB, Bray M, Ozato K (2009) Ebola Zaire virus blocks type I interferon production by exploiting the host SUMO modification machinery. PLoS Pathog 5(6):e1000493. doi:10.1371/journal.ppat.1000493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chertow DS, Kleine C, Edwards JK, Scaini R, Giuliani R, Sprecher A (2014) Ebola virus disease in West Africa–clinical manifestations and management. The N Engl J Med 371(22):2054–2057. doi:10.1056/NEJMp1413084

    Article  PubMed  Google Scholar 

  • 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(17):9060–9068. doi:10.1128/JVI.00659-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Connolly BM, Steele KE, Davis KJ, Geisbert TW, Kell WM, Jaax NK, Jahrling PB (1999) Pathogenesis of experimental Ebola virus infection in guinea pigs. J Infect Dis 179(Suppl 1):S203–S217. doi:10.1086/514305

    Article  PubMed  Google Scholar 

  • Cote M, Misasi J, Ren T, Bruchez A, Lee K, Filone CM, Hensley L, Li Q, Ory D, Chandran K, Cunningham J (2011) Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus infection. Nature 477(7364):344–348. doi:10.1038/nature10380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cross RW, Fenton KA, Geisbert JB, Mire CE, Geisbert TW (2015) Modeling the disease course of Zaire ebolavirus infection in the outbred guinea pig. J Infect Dis 212(Suppl 2):S305–S315. doi:10.1093/infdis/jiv237

    Article  CAS  PubMed  Google Scholar 

  • Cross RW, Mire CE, Borisevich V, Geisbert JB, Fenton KA, Geisbert TW (2016) The domestic ferret (Mustela putorius furo) as a Lethal Infection Model for 3 Species of Ebolavirus. J Infect Dis 214(4):565–569. doi:10.1093/infdis/jiw209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dahlke C, Lunemann S, Kasonta R, Kreuels B, Schmiedel S, Ly ML, Fehling SK, Strecker T, Becker S, Altfeld M, Sow A, Lohse AW, Munoz-Fontela C, Addo MM (2016) Comprehensive characterization of cellular immune responses following Ebola virus infection. J Infect Dis. doi:10.1093/infdis/jiw508

    Article  Google Scholar 

  • Dahlmann F, Biedenkopf N, Babler A, Jahnen-Dechent W, Karsten CB, Gnirss K, Schneider H, Wrensch F, O’Callaghan CA, Bertram S, Herrler G, Becker S, Pohlmann S, Hofmann-Winkler H (2015) Analysis of Ebola Virus Entry Into Macrophages. J Infect Dis 212(Suppl 2):S247–S257. doi:10.1093/infdis/jiv140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dallatomasina S, Crestani R, Sylvester Squire J, Declerk H, Caleo GM, Wolz A, Stinson K, Patten G, Brechard R, Gbabai OB, Spreicher A, Van Herp M, Zachariah R (2015) Ebola outbreak in rural West Africa: epidemiology, clinical features and outcomes. Tropical medicine & international health: TM & IH 20(4):448–454. doi:10.1111/tmi.12454

    Article  Google Scholar 

  • Dietz PM, Jambai A, Paweska JT, Yoti Z, Ksiazek TG (2015) Epidemiology and risk factors for Ebola virus disease in Sierra Leone-23 May 2014–31 January 2015. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 61(11):1648–1654. doi:10.1093/cid/civ568

    Article  Google Scholar 

  • Dolnik O, Volchkova V, Garten W, Carbonnelle C, Becker S, Kahnt J, Stroher U, Klenk HD, Volchkov V (2004) Ectodomain shedding of the glycoprotein GP of Ebola virus. EMBO J 23(10):2175–2184. doi:10.1038/sj.emboj.7600219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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–S328. doi:10.1093/infdis/jiv268

    Article  CAS  PubMed  Google Scholar 

  • Dube D, Schornberg KL, Shoemaker CJ, Delos SE, Stantchev TS, Clouse KA, Broder CC, White JM (2010) Cell adhesion-dependent membrane trafficking of a binding partner for the ebolavirus glycoprotein is a determinant of viral entry. Proc Natl Acad Sci USA 107(38):16637–16642. doi:10.1073/pnas.1008509107

    Article  PubMed  Google Scholar 

  • Ebihara H, Takada A, Kobasa D, Jones S, Neumann G, Theriault S, Bray M, Feldmann H, Kawaoka Y (2006) Molecular determinants of Ebola virus virulence in mice. PLoS Pathog 2(7):e73. doi:10.1371/journal.ppat.0020073

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ebihara H, Rockx B, Marzi A, Feldmann F, Haddock E, Brining D, LaCasse RA, Gardner D, Feldmann H (2011) Host response dynamics following lethal infection of rhesus macaques with Zaire ebolavirus. J Infect Dis 204(Suppl 3):S991–S999. doi:10.1093/infdis/jir336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ebihara H, Zivcec M, Gardner D, Falzarano D, LaCasse R, Rosenke R, Long D, Haddock E, Fischer E, Kawaoka Y, Feldmann H (2013) A Syrian golden hamster model recapitulating ebola hemorrhagic fever. J Infect Dis 207(2):306–318. doi:10.1093/infdis/jis626

    Article  CAS  PubMed  Google Scholar 

  • Edwards MR, Basler CF (2015) Marburg virus VP24 protein relieves suppression of the NF-kappaB Pathway Through Interaction With Kelch-like ECH-Associated Protein 1. J Infect Dis 212(Suppl 2):S154–S159. doi:10.1093/infdis/jiv050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Edwards MR, Liu G, Mire CE, Sureshchandra S, Luthra P, Yen B, Shabman RS, Leung DW, Messaoudi I, Geisbert TW, Amarasinghe GK, Basler CF (2016) Differential regulation of interferon responses by Ebola and Marburg virus VP35 proteins. Cell Rep 14(7):1632–1640. doi:10.1016/j.celrep.2016.01.049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Empig CJ, Goldsmith MA (2002) Association of the caveola vesicular system with cellular entry by filoviruses. J Virol 76(10):5266–5270

    Article  CAS  Google Scholar 

  • 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(11):e1004509. doi:10.1371/journal.ppat.1004509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Favier AL, Gout E, Reynard O, Ferraris O, Kleman JP, Volchkov V, Peyrefitte C, Thielens NM (2016) Enhancement of ebola virus infection via Ficolin-1 Interaction with the mucin domain of GP glycoprotein. J Virol 90(11):5256–5269. doi:10.1128/JVI.00232-16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feagins AR, Basler CF (2015) Lloviu virus VP24 and VP35 proteins function as innate immune antagonists in human and bat cells. Virology 485:145–152. doi:10.1016/j.virol.2015.07.010

    Article  CAS  PubMed  Google Scholar 

  • Fisher-Hoch SP, Brammer TL, Trappier SG, Hutwagner LC, Farrar BB, Ruo SL, Brown BG, Hermann LM, Perez-Oronoz GI, Goldsmith CS et al (1992a) Pathogenic potential of filoviruses: role of geographic origin of primate host and virus strain. J Infect Dis 166(4):753–763

    Article  CAS  Google Scholar 

  • Fisher-Hoch SP, Perez-Oronoz GI, Jackson EL, Hermann LM, Brown BG (1992b) Filovirus clearance in non-human primates. Lancet 340(8817):451–453

    Article  CAS  Google Scholar 

  • Fitzgerald F, Naveed A, Wing K, Gbessay M, Ross JC, Checchi F, Youkee D, Jalloh MB, Baion D, Mustapha A, Jah H, Lako S, Oza S, Boufkhed S, Feury R, Bielicki JA, Gibb DM, Klein N, Sahr F, Yeung S (2016) Ebola virus disease in children, sierra leone, 2014–2015. Emerg Infect Dis 22(10):1769–1777. doi:10.3201/eid2210.160579

    Article  PubMed  PubMed Central  Google Scholar 

  • Fitzpatrick G, Vogt F, Moi Gbabai OB, Decroo T, Keane M, De Clerck H, Grolla A, Brechard R, Stinson K, Van Herp M (2015) The contribution of ebola viral load at admission and other patient characteristics to mortality in a Medecins Sans Frontieres Ebola Case Management Centre, Kailahun, Sierra Leone, June–October 2014. J Infect Dis 212(11):1752–1758. doi:10.1093/infdis/jiv304

    Article  PubMed  PubMed Central  Google Scholar 

  • Flyak AI, Shen X, Murin CD, Turner HL, David JA, Fusco ML, Lampley R, Kose N, Ilinykh PA, Kuzmina N, Branchizio A, King H, Brown L, Bryan C, Davidson E, Doranz BJ, Slaughter JC, Sapparapu G, Klages C, Ksiazek TG, Saphire EO, Ward AB, Bukreyev A, Crowe JE Jr (2016) Cross-reactive and potent neutralizing antibody responses in human survivors of natural ebolavirus infection. Cell 164(3):392–405. doi:10.1016/j.cell.2015.12.022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(9):e1001098. doi:10.1371/journal.ppat.1001098

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gabriel G, Feldmann F, Reimer R, Thiele S, Fischer M, Hartmann E, Bader M, Ebihara H, Hoenen T, Feldmann H (2015) Importin-alpha7 is involved in the formation of ebola virus inclusion bodies but is not essential for pathogenicity in mice. J Infect Dis 212(Suppl 2):S316–S321. doi:10.1093/infdis/jiv240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Garcia-Dorival I, Wu W, Dowall S, Armstrong S, Touzelet O, Wastling J, Barr JN, Matthews D, Carroll M, Hewson R, Hiscox JA (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(11):5120–5135. doi:10.1021/pr500556d

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Dorival I, Wu W, Armstrong SD, Barr JN, Carroll MW, Hewson R, Hiscox JA (2016) Elucidation of the cellular interactome of the Ebolavirus nucleoprotein and identification of therapeutic targets. J Proteome Res. doi:10.1021/acs.jproteome.6b00337

    Article  PubMed  Google Scholar 

  • Gc JB, Gerstman BS, Stahelin RV, Chapagain PP (2016) The Ebola virus protein VP40 hexamer enhances the clustering of PI(4,5)P2 lipids in the plasma membrane. Phys Chem Chem Phys 18(41):28409–28417. doi:10.1039/c6cp03776c

    Article  PubMed  PubMed Central  Google Scholar 

  • 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(2):171–186

    Article  CAS  Google Scholar 

  • Geisbert TW, Hensley LE, Jahrling PB, Larsen T, Geisbert JB, Paragas J, Young HA, Fredeking TM, Rote WE, Vlasuk GP (2003a) Treatment of Ebola virus infection with a recombinant inhibitor of factor VIIa/tissue factor: a study in rhesus monkeys. Lancet 362(9400):1953–1958. doi:10.1016/S0140-6736(03)15012-X

    Article  CAS  PubMed  Google Scholar 

  • Geisbert TW, Hensley LE, Larsen T, Young HA, Reed DS, Geisbert JB, Scott DP, Kagan E, Jahrling PB, Davis KJ (2003b) Pathogenesis of Ebola hemorrhagic fever in cynomolgus macaques: evidence that dendritic cells are early and sustained targets of infection. Am J Pathol 163(6):2347–2370. doi:10.1016/S0002-9440(10)63591-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Geisbert TW, Young HA, Jahrling PB, Davis KJ, Kagan E, Hensley LE (2003c) Mechanisms underlying coagulation abnormalities in ebola hemorrhagic fever: overexpression of tissue factor in primate monocytes/macrophages is a key event. J Infect Dis 188(11):1618–1629. doi:10.1086/379724

    Article  CAS  PubMed  Google Scholar 

  • Geisbert TW, Young HA, Jahrling PB, Davis KJ, Larsen T, Kagan E, Hensley LE (2003d) 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(6):2371–2382. doi:10.1016/S0002-9440(10)63592-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Georges AJ, Leroy EM, Renaut AA, Benissan CT, Nabias RJ, Ngoc MT, Obiang PI, Lepage JP, Bertherat EJ, Benoni DD, Wickings EJ, Amblard JP, Lansoud-Soukate JM, Milleliri JM, Baize S, Georges-Courbot MC (1999) Ebola hemorrhagic fever outbreaks in Gabon, 1994–1997: epidemiologic and health control issues. J Infect Dis 179(Suppl 1):S65–S75. doi:10.1086/514290

    Article  PubMed  Google Scholar 

  • Gibb TR, Bray M, Geisbert TW, Steele KE, Kell WM, Davis KJ, Jaax NK (2001) Pathogenesis of experimental Ebola Zaire virus infection in BALB/c mice. J Comp Pathol 125(4):233–242. doi:10.1053/jcpa.2001.0502

    Article  CAS  PubMed  Google Scholar 

  • Gnirss K, Fiedler M, Kramer-Kuhl A, Bolduan S, Mittler E, Becker S, Schindler M, Pohlmann S (2014) Analysis of determinants in filovirus glycoproteins required for tetherin antagonism. Viruses 6(4):1654–1671. doi:10.3390/v6041654

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gregory SM, Harada E, Liang B, Delos SE, White JM, Tamm LK (2011) Structure and function of the complete internal fusion loop from Ebolavirus glycoprotein 2. Proc Natl Acad Sci USA 108(27):11211–11216. doi:10.1073/pnas.1104760108

    Article  PubMed  Google Scholar 

  • Gregory SM, Larsson P, Nelson EA, Kasson PM, White JM, Tamm LK (2014) Ebolavirus entry requires a compact hydrophobic fist at the tip of the fusion loop. J Virol 88(12):6636–6649. doi:10.1128/JVI.00396-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Groseth A, Charton JE, Sauerborn M, Feldmann F, Jones SM, Hoenen T, Feldmann H (2009) The Ebola virus ribonucleoprotein complex: a novel VP30-L interaction identified. Virus Res 140(1–2):8–14. doi:10.1016/j.virusres.2008.10.017

    Article  CAS  PubMed  Google Scholar 

  • Gupta M, Spiropoulou C, Rollin PE (2007) Ebola virus infection of human PBMCs causes massive death of macrophages, CD4 and CD8 T cell sub-populations in vitro. Virology 364(1):45–54. doi:10.1016/j.virol.2007.02.017

    Article  CAS  PubMed  Google Scholar 

  • 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. doi:10.1093/infdis/jiv125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haaskjold YL, Bolkan HA, Krogh KO, Jongopi J, Lundeby KM, Mellesmo S, Garces PS, Josendal O, Opstad A, Svensen E, Fuentes LM, Kamara AS, Riera M, Arranz J, Roberts DP, Stamper PD, Austin P, Moosa AJ, Marke D, Hassan S, Eide GE, Berg A, Blomberg B (2016) Clinical features of and risk factors for fatal ebola virus disease, Moyamba District, Sierra Leone, December 2014–February 2015. Emerg Infect Dis 22(9):1537–1544. doi:10.3201/eid2209.151621

    Article  PubMed  PubMed Central  Google Scholar 

  • Hacke M, Bjorkholm P, Hellwig A, Himmels P, de Almodovar CR, Brugger B, Wieland F, Ernst AM (2015) Inhibition of Ebola virus glycoprotein-mediated cytotoxicity by targeting its transmembrane domain and cholesterol. Nat Commun 6:7688. doi:10.1038/ncomms8688

    Article  PubMed  Google Scholar 

  • Halfmann P, Neumann G, Kawaoka Y (2011) The Ebolavirus VP24 protein blocks phosphorylation of p38 mitogen-activated protein kinase. J Infect Dis 204(Suppl 3):S953–S956. doi:10.1093/infdis/jir325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Han Z, Harty RN (2005) Packaging of actin into Ebola virus VLPs. Virol J 2:92. doi:10.1186/1743-422X-2-92

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Han Z, Harty RN (2007) Influence of calcium/calmodulin on budding of Ebola VLPs: implications for the involvement of the Ras/Raf/MEK/ERK pathway. Virus Genes 35(3):511–520. doi:10.1007/s11262-007-0125-9

    Article  CAS  PubMed  Google Scholar 

  • Han Z, Madara JJ, Herbert A, Prugar LI, Ruthel G, Lu J, Liu Y, Liu W, Liu X, Wrobel JE, Reitz AB, Dye JM, Harty RN, Freedman BD (2015a) Calcium regulation of hemorrhagic fever virus budding: Mechanistic implications for host-oriented therapeutic intervention. PLoS Pathog 11(10):e1005220. doi:10.1371/journal.ppat.1005220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Han Z, Madara JJ, Liu Y, Liu W, Ruthel G, Freedman BD, Harty RN (2015b) 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 2):S138–S145. doi:10.1093/infdis/jiu838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Han Z, Sagum CA, Bedford MT, Sidhu SS, Sudol M, Harty RN (2016) ITCH E3 ubiquitin ligase interacts with ebola virus VP40 to regulate budding. J Virol 90(20):9163–9171. doi:10.1128/JVI.01078-16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hartman AL, Bird BH, Towner JS, Antoniadou ZA, Zaki SR, Nichol ST (2008) Inhibition of IRF-3 activation by VP35 is critical for the high level of virulence of ebola virus. J Virol 82(6):2699–2704. doi:10.1128/JVI.02344-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hensley LE, Young HA, Jahrling PB, Geisbert TW (2002) Proinflammatory response during Ebola virus infection of primate models: possible involvement of the tumor necrosis factor receptor superfamily. Immunol Lett 80(3):169–179

    Article  CAS  Google Scholar 

  • Hensley LE, Stevens EL, Yan SB, Geisbert JB, Macias WL, Larsen T, Daddario-DiCaprio KM, Cassell GH, Jahrling PB, Geisbert TW (2007) Recombinant human activated protein C for the postexposure treatment of Ebola hemorrhagic fever. J Infect Dis 196(Suppl 2):S390–S399. doi:10.1086/520598

    Article  CAS  PubMed  Google Scholar 

  • Hoenen T, Shabman RS, Groseth A, Herwig A, Weber M, Schudt G, Dolnik O, Basler CF, Becker S, Feldmann H (2012) Inclusion bodies are a site of ebolavirus replication. J Virol 86(21):11779–11788. doi:10.1128/JVI.01525-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoffmann M, Gonzalez Hernandez M, Berger E, Marzi A, Pohlmann S (2016) The glycoproteins of all filovirus species use the same host factors for entry into bat and human cells but entry efficiency is species dependent. PLoS ONE 11(2):e0149651. doi:10.1371/journal.pone.0149651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang Y, Xu L, Sun Y, Nabel GJ (2002) The assembly of Ebola virus nucleocapsid requires virion-associated proteins 35 and 24 and posttranslational modification of nucleoprotein. Mol Cell 10(2):307–316

    Article  Google Scholar 

  • Huang IC, Bailey CC, Weyer JL, Radoshitzky SR, Becker MM, Chiang JJ, Brass AL, Ahmed AA, Chi X, Dong L, Longobardi LE, Boltz D, Kuhn JH, Elledge SJ, Bavari S, Denison MR, Choe H, Farzan M (2011) Distinct patterns of IFITM-mediated restriction of filoviruses, SARS coronavirus, and influenza A virus. PLoS Pathog 7(1):e1001258. doi:10.1371/journal.ppat.1001258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hunt CL, Kolokoltsov AA, Davey RA, Maury W (2011) The Tyro3 receptor kinase Axl enhances macropinocytosis of Zaire ebolavirus. J Virol 85(1):334–347. doi:10.1128/JVI.01278-09

    Article  CAS  PubMed  Google Scholar 

  • Ilinykh PA, Tigabu B, Ivanov A, Ammosova T, Obukhov Y, Garron T, Kumari N, Kovalskyy D, Platonov MO, Naumchik VS, Freiberg AN, Nekhai S, Bukreyev A (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(33):22723–22738. doi:10.1074/jbc.M114.575050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ilinykh PA, Lubaki NM, Widen SG, Renn LA, Theisen TC, Rabin RL, Wood TG, Bukreyev A (2015) Different temporal effects of ebola virus VP35 and VP24 proteins on global gene expression in human dendritic cells. J Virol 89(15):7567–7583. doi:10.1128/JVI.00924-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iwasa A, Halfmann P, Noda T, Oyama M, Kozuka-Hata H, Watanabe S, Shimojima M, Watanabe T, Kawaoka Y (2011) Contribution of Sec61alpha to the life cycle of Ebola virus. J Infect Dis 204(Suppl 3):S919–S926. doi:10.1093/infdis/jir324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jasenosky LD, Neumann G, Lukashevich I, Kawaoka Y (2001) Ebola virus VP40-induced particle formation and association with the lipid bilayer. J Virol 75(11):5205–5214. doi:10.1128/JVI.75.11.5205-5214.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jemielity S, Wang JJ, Chan YK, Ahmed AA, Li W, Monahan S, Bu X, Farzan M, Freeman GJ, Umetsu DT, Dekruyff RH, Choe H (2013) TIM-family proteins promote infection of multiple enveloped viruses through virion-associated phosphatidylserine. PLoS Pathog 9(3):e1003232. doi:10.1371/journal.ppat.1003232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ji X, Olinger GG, Aris S, Chen Y, Gewurz H, Spear GT (2005) Mannose-binding lectin binds to Ebola and Marburg envelope glycoproteins, resulting in blocking of virus interaction with DC-SIGN and complement-mediated virus neutralization. J Gen Virol 86(Pt 9):2535–2542. doi:10.1099/vir.0.81199-0

    Article  CAS  PubMed  Google Scholar 

  • Jin H, Yan Z, Prabhakar BS, Feng Z, Ma Y, Verpooten D, Ganesh B, He B (2010) The VP35 protein of Ebola virus impairs dendritic cell maturation induced by virus and lipopolysaccharide. J Gen Virol 91(Pt 2):352–361. doi:10.1099/vir.0.017343-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Johnson KA, Taghon GJ, Scott JL, Stahelin RV (2016) The Ebola Virus matrix protein, VP40, requires phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) for extensive oligomerization at the plasma membrane and viral egress. Sci Rep 6:19125. doi:10.1038/srep19125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaletsky RL, Simmons G, Bates P (2007) Proteolysis of the Ebola virus glycoproteins enhances virus binding and infectivity. J Virol 81(24):13378–13384. doi:10.1128/JVI.01170-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 USA 106(8):2886–2891. doi:10.1073/pnas.0811014106

    Article  PubMed  Google Scholar 

  • Kash JC, Muhlberger E, Carter V, Grosch M, Perwitasari O, Proll SC, Thomas MJ, Weber F, Klenk HD, Katze MG (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(6):3009–3020. doi:10.1128/JVI.80.6.3009-3020.2006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khan AS, Tshioko FK, Heymann DL, Le Guenno B, Nabeth P, Kerstiens B, Fleerackers Y, Kilmarx PH, Rodier GR, Nkuku O, Rollin PE, Sanchez A, Zaki SR, Swanepoel R, Tomori O, Nichol ST, Peters CJ, Muyembe-Tamfum JJ, Ksiazek TG (1999) The reemergence of Ebola hemorrhagic fever, Democratic Republic of the Congo, 1995. Commission de Lutte contre les Epidemies a Kikwit. The Journal of infectious diseases 179 Suppl 1:S76-86. doi:10.1086/514306

    Article  Google Scholar 

  • Kimberlin CR, Bornholdt ZA, Li S, Woods VL Jr, MacRae IJ, Saphire EO (2010) Ebolavirus VP35 uses a bimodal strategy to bind dsRNA for innate immune suppression. Proc Natl Acad Sci USA 107(1):314–319. doi:10.1073/pnas.0910547107

    Article  PubMed  Google Scholar 

  • Kindrachuk J, Wahl-Jensen V, Safronetz D, Trost B, Hoenen T, Arsenault R, Feldmann F, Traynor D, Postnikova E, Kusalik A, Napper S, Blaney JE, Feldmann H, Jahrling PB (2014) Ebola virus modulates transforming growth factor beta signaling and cellular markers of mesenchyme-like transition in hepatocytes. J Virol 88(17):9877–9892. doi:10.1128/JVI.01410-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kondratowicz AS, Lennemann NJ, Sinn PL, Davey RA, Hunt CL, Moller-Tank S, Meyerholz DK, Rennert P, Mullins RF, Brindley M, Sandersfeld LM, Quinn K, Weller M, McCray PB Jr, Chiorini J, Maury W (2011) T-cell immunoglobulin and mucin domain 1 (TIM-1) is a receptor for Zaire Ebolavirus and Lake Victoria Marburgvirus. Proc Natl Acad Sci USA 108(20):8426–8431. doi:10.1073/pnas.1019030108

    Article  PubMed  Google Scholar 

  • Kozak R, He S, Kroeker A, de La Vega MA, Audet J, Wong G, Urfano C, Antonation K, Embury-Hyatt C, Kobinger GP, Qiu X (2016) Ferrets infected with bundibugyo virus or ebola virus recapitulate important aspects of human filovirus disease. J Virol 90(20):9209–9223. doi:10.1128/JVI.01033-16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kratz T, Roddy P, Tshomba Oloma A, Jeffs B, Pou Ciruelo D, de la Rosa O, Borchert M (2015) Ebola virus disease outbreak in Isiro, Democratic Republic of the Congo, 2012: Signs and Symptoms. Management and Outcomes. PloS one 10(6):e0129333. doi:10.1371/journal.pone.0129333

    Article  CAS  PubMed  Google Scholar 

  • Kubota T, Matsuoka M, Chang TH, Bray M, Jones S, Tashiro M, Kato A, Ozato K (2009) Ebolavirus VP35 interacts with the cytoplasmic dynein light chain 8. J Virol 83(13):6952–6956. doi:10.1128/JVI.00480-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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. doi:10.1093/infdis/jir378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kuroda M, Fujikura D, Nanbo A, Marzi A, Noyori O, Kajihara M, Maruyama J, Matsuno K, Miyamoto H, Yoshida R, Feldmann H, Takada A (2015) Interaction between TIM-1 and NPC1 is important for cellular entry of ebola virus. J Virol 89(12):6481–6493. doi:10.1128/JVI.03156-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lado M, Walker NF, Baker P, Haroon S, Brown CS, Youkee D, Studd N, Kessete Q, Maini R, Boyles T, Hanciles E, Wurie A, Kamara TB, Johnson O, Leather AJ (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(9):1024–1033. doi:10.1016/S1473-3099(15)00137-1

    Article  PubMed  Google Scholar 

  • Le Guenno B, Formenty P, Wyers M, Gounon P, Walker F, Boesch C (1995) Isolation and partial characterisation of a new strain of Ebola virus. Lancet 345(8960):1271–1274

    Article  Google Scholar 

  • 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(1):e00862–e00813. doi:10.1128/mBio.00862-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leung DW, Ginder ND, Fulton DB, Nix J, Basler CF, Honzatko RB, Amarasinghe GK (2009) Structure of the Ebola VP35 interferon inhibitory domain. Proc Natl Acad Sci USA 106(2):411–416. doi:10.1073/pnas.0807854106

    Article  PubMed  Google Scholar 

  • Leung DW, Prins KC, Borek DM, Farahbakhsh M, Tufariello JM, Ramanan P, Nix JC, Helgeson LA, Otwinowski Z, Honzatko RB, Basler CF, Amarasinghe GK (2010) Structural basis for dsRNA recognition and interferon antagonism by Ebola VP35. Nat Struct Mol Biol 17(2):165–172. doi:10.1038/nsmb.1765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leung LW, Martinez O, Reynard O, Volchkov VE, Basler CF (2011a) Ebola virus failure to stimulate plasmacytoid dendritic cell interferon responses correlates with impaired cellular entry. J Infect Dis 204(Suppl 3):S973–S977. doi:10.1093/infdis/jir331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leung LW, Park MS, Martinez O, Valmas C, Lopez CB, Basler CF (2011b) Ebolavirus VP35 suppresses IFN production from conventional but not plasmacytoid dendritic cells. Immunol Cell Biol 89(7):792–802. doi:10.1038/icb.2010.169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Licata JM, Simpson-Holley M, Wright NT, Han Z, Paragas J, Harty RN (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(3):1812–1819

    Article  CAS  Google Scholar 

  • Liddell AM, Davey RT Jr, Mehta AK, Varkey JB, Kraft CS, Tseggay GK, Badidi O, Faust AC, Brown KV, Suffredini AF, Barrett K, Wolcott MJ, Marconi VC, Lyon GM 3rd, Weinstein GL, Weinmeister K, Sutton S, Hazbun M, Albarino CG, Reed Z, Cannon D, Stroher U, Feldman M, Ribner BS, Lane HC, Fauci AS, Uyeki TM (2015) Characteristics and clinical management of a cluster of 3 patients with ebola virus disease, including the first domestically acquired cases in the United States. Ann Intern Med 163(2):81–90. doi:10.7326/M15-0530

    Article  PubMed  PubMed Central  Google Scholar 

  • Lin G, Simmons G, Pohlmann S, Baribaud F, Ni H, Leslie GJ, Haggarty BS, Bates P, Weissman D, Hoxie JA, Doms RW (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(2):1337–1346

    Article  CAS  Google Scholar 

  • Liu SY, Aliyari R, Chikere K, Li G, Marsden MD, Smith JK, Pernet O, Guo H, Nusbaum R, Zack JA, Freiberg AN, Su L, Lee B, Cheng G (2013) Interferon-inducible cholesterol-25-hydroxylase broadly inhibits viral entry by production of 25-hydroxycholesterol. Immunity 38(1):92–105. doi:10.1016/j.immuni.2012.11.005

    Article  CAS  PubMed  Google Scholar 

  • Lu J, Qu Y, Liu Y, Jambusaria R, Han Z, Ruthel G, Freedman BD, Harty RN (2013) Host IQGAP1 and Ebola virus VP40 interactions facilitate virus-like particle egress. J Virol 87(13):7777–7780. doi:10.1128/JVI.00470-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu HJ, Qian J, Kargbo D, Zhang XG, Yang F, Hu Y, Sun Y, Cao YX, Deng YQ, Su HX, Dafae F, Sun Y, Wang CY, Nie WM, Bai CQ, Xia ZP, Liu K, Kargbo B, Gao GF, Jiang JF (2015) Ebola virus outbreak investigation, Sierra Leone, September 28–November 11 2014. Emerg Infect Dis 21(11):1921–1927. doi:10.3201/eid2111.150582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lubaki NM, Ilinykh P, Pietzsch C, Tigabu B, Freiberg AN, Koup RA, Bukreyev A (2013) The lack of maturation of Ebola virus-infected dendritic cells results from the cooperative effect of at least two viral domains. J Virol 87(13):7471–7485. doi:10.1128/JVI.03316-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ludtke A, Ruibal P, Becker-Ziaja B, Rottstegge M, Wozniak DM, Cabeza-Cabrerizo M, Thorenz A, Weller R, Kerber R, Idoyaga J, Magassouba N, Gabriel M, Gunther S, Oestereich L, Munoz-Fontela C (2016) Ebola virus disease is characterized by poor activation and reduced levels of circulating cd16 + monocytes. J Infect Dis 214(suppl 3):S275–S280. doi:10.1093/infdis/jiw260

    Article  CAS  PubMed  Google Scholar 

  • Luthra P, Ramanan P, Mire CE, Weisend C, Tsuda Y, Yen B, Liu G, Leung DW, Geisbert TW, Ebihara H, Amarasinghe GK, Basler CF (2013) Mutual antagonism between the Ebola virus VP35 protein and the RIG-I activator PACT determines infection outcome. Cell Host Microbe 14(1):74–84. doi:10.1016/j.chom.2013.06.010

    Article  CAS  PubMed  Google Scholar 

  • Luthra P, Jordan DS, Leung DW, Amarasinghe GK, Basler CF (2015) Ebola virus VP35 interaction with dynein LC8 regulates viral RNA synthesis. J Virol 89(9):5148–5153. doi:10.1128/JVI.03652-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • MacNeil A, Farnon EC, Wamala J, Okware S, Cannon DL, Reed Z, Towner JS, Tappero JW, Lutwama J, Downing R, Nichol ST, Ksiazek TG, Rollin PE (2010) Proportion of deaths and clinical features in Bundibugyo Ebola virus infection. Uganda Emerg Infect Dis 16(12):1969–1972. doi:10.3201/eid1612.100627

    Article  PubMed  Google Scholar 

  • Markosyan RM, Miao C, Zheng YM, Melikyan GB, Liu SL, Cohen FS (2016) Induction of cell-cell fusion by Ebola virus glycoprotein: low pH Is not a trigger. PLoS Pathog 12(1):e1005373. doi:10.1371/journal.ppat.1005373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martinez O, Valmas C, Basler CF (2007) Ebola virus-like particle-induced activation of NF-kappaB and Erk signaling in human dendritic cells requires the glycoprotein mucin domain. Virology 364(2):342–354. doi:10.1016/j.virol.2007.03.020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martinez MJ, Volchkova VA, Raoul H, Alazard-Dany N, Reynard O, Volchkov VE (2011) Role of VP30 phosphorylation in the Ebola virus replication cycle. J Infect Dis 204(Suppl 3):S934–S940. doi:10.1093/infdis/jir320

    Article  CAS  PubMed  Google Scholar 

  • Martinez O, Johnson JC, Honko A, Yen B, Shabman RS, Hensley LE, Olinger GG, Basler CF (2013) Ebola virus exploits a monocyte differentiation program to promote its entry. J Virol 87(7):3801–3814. doi:10.1128/JVI.02695-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martins K, Cooper C, Warren T, Wells J, Bell T, Raymond J, Stuthman K, Benko J, Garza N, van Tongeren S, Donnelly G, Retterer C, Dong L, Bavari S (2015) Characterization of clinical and immunological parameters during Ebola virus infection of rhesus macaques. Viral Immunol 28(1):32–41. doi:10.1089/vim.2014.0085

    Article  CAS  PubMed  Google Scholar 

  • Martin-Serrano J, Zang T, Bieniasz PD (2001) HIV-1 and Ebola virus encode small peptide motifs that recruit Tsg101 to sites of particle assembly to facilitate egress. Nat Med 7(12):1313–1319. doi:10.1038/nm1201-1313

    Article  CAS  PubMed  Google Scholar 

  • Marzi A, Akhavan A, Simmons G, Gramberg T, Hofmann H, Bates P, Lingappa VR, Pohlmann S (2006) The signal peptide of the ebolavirus glycoprotein influences interaction with the cellular lectins DC-SIGN and DC-SIGNR. J Virol 80(13):6305–6317. doi:10.1128/JVI.02545-05

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marzi A, Moller P, Hanna SL, Harrer T, Eisemann J, Steinkasserer A, Becker S, Baribaud F, Pohlmann S (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 2):S237–S246. doi:10.1086/520607

    Article  CAS  PubMed  Google Scholar 

  • Marzi A, Reinheckel T, Feldmann H (2012) Cathepsin B & L are not required for ebola virus replication. PLoS neglected tropical diseases 6(12):e1923. doi:10.1371/journal.pntd.0001923

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mateo M, Reid SP, Leung LW, Basler CF, Volchkov VE (2010) Ebolavirus VP24 binding to karyopherins is required for inhibition of interferon signaling. J Virol 84(2):1169–1175. doi:10.1128/JVI.01372-09

    Article  CAS  PubMed  Google Scholar 

  • Mateo M, Carbonnelle C, Martinez MJ, Reynard O, Page A, Volchkova VA, Volchkov VE (2011a) Knockdown of Ebola virus VP24 impairs viral nucleocapsid assembly and prevents virus replication. J Infect Dis 204(Suppl 3):S892–S896. doi:10.1093/infdis/jir311

    Article  CAS  PubMed  Google Scholar 

  • Mateo M, Carbonnelle C, Reynard O, Kolesnikova L, Nemirov K, Page A, Volchkova VA, Volchkov VE (2011b) VP24 is a molecular determinant of Ebola virus virulence in guinea pigs. J Infect Dis 204(Suppl 3):S1011–S1020. doi:10.1093/infdis/jir338

    Article  CAS  PubMed  Google Scholar 

  • Matsuno K, Nakayama E, Noyori O, Marzi A, Ebihara H, Irimura T, Feldmann H, Takada A (2010) C-type lectins do not act as functional receptors for filovirus entry into cells. Biochem Biophys Res Commun 403(1):144–148. doi:10.1016/j.bbrc.2010.10.136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McElroy AK, Akondy RS, Davis CW, Ellebedy AH, Mehta AK, Kraft CS, Lyon GM, Ribner BS, Varkey J, Sidney J, Sette A, Campbell S, Stroher U, Damon I, Nichol ST, Spiropoulou CF, Ahmed R (2015) Human Ebola virus infection results in substantial immune activation. Proc Natl Acad Sci USA 112(15):4719–4724. doi:10.1073/pnas.1502619112

    Article  CAS  PubMed  Google Scholar 

  • Mehedi M, Hoenen T, Robertson S, Ricklefs S, Dolan MA, Taylor T, Falzarano D, Ebihara H, Porcella SF, Feldmann H (2013) Ebola virus RNA editing depends on the primary editing site sequence and an upstream secondary structure. PLoS Pathog 9(10):e1003677. doi:10.1371/journal.ppat.1003677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Melanson VR, Kalina WV, Williams P (2015) Ebola virus infection induces irregular dendritic cell gene expression. Viral Immunol 28(1):42–50. doi:10.1089/vim.2014.0091

    Article  CAS  PubMed  Google Scholar 

  • Miao C, Li M, Zheng YM, Cohen FS, Liu SL (2016) Cell-cell contact promotes Ebola virus GP-mediated infection. Virology 488:202–215. doi:10.1016/j.virol.2015.11.019

    Article  CAS  PubMed  Google Scholar 

  • Mingo RM, Simmons JA, Shoemaker CJ, Nelson EA, Schornberg KL, D’Souza RS, Casanova JE, White JM (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(5):2931–2943. doi:10.1128/JVI.03398-14

    Article  CAS  PubMed  Google Scholar 

  • Misasi J, Chandran K, Yang JY, Considine B, Filone CM, Cote M, Sullivan N, Fabozzi G, Hensley L, Cunningham J (2012) Filoviruses require endosomal cysteine proteases for entry but exhibit distinct protease preferences. J Virol 86(6):3284–3292. doi:10.1128/JVI.06346-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Modrof J, Muhlberger E, Klenk HD, Becker S (2002) Phosphorylation of VP30 impairs ebola virus transcription. J Biol Chem 277(36):33099–33104. doi:10.1074/jbc.M203775200

    Article  CAS  PubMed  Google Scholar 

  • Mohamadzadeh M, Coberley SS, Olinger GG, Kalina WV, Ruthel G, Fuller CL, Swenson DL, Pratt WD, Kuhns DB, Schmaljohn AL (2006) Activation of triggering receptor expressed on myeloid cells-1 on human neutrophils by marburg and ebola viruses. J Virol 80(14):7235–7244. doi:10.1128/JVI.00543-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(12):e1003065. doi:10.1371/journal.ppat.1003065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(2):1205–1217. doi:10.1128/JVI.01810-14

    Article  CAS  PubMed  Google Scholar 

  • Moller-Tank S, Kondratowicz AS, Davey RA, Rennert PD, Maury W (2013) Role of the phosphatidylserine receptor TIM-1 in enveloped-virus entry. J Virol 87(15):8327–8341. doi:10.1128/JVI.01025-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moole H, Chitta S, Victor D, Kandula M, Moole V, Ghadiam H, Akepati A, Yerasi C, Uppu A, Dharmapuri S, Boddireddy R, Fischer J, Lynch T (2015) Association of clinical signs and symptoms of Ebola viral disease with case fatality: a systematic review and meta-analysis. J Community Hosp Intern Med Perspect 5(4):28406. doi:10.3402/jchimp.v5.28406

    Article  PubMed  Google Scholar 

  • Morizono K, Chen IS (2014) Role of phosphatidylserine receptors in enveloped virus infection. J Virol 88(8):4275–4290. doi:10.1128/JVI.03287-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Muhlberger E, Weik M, Volchkov VE, Klenk HD, Becker S (1999) Comparison of the transcription and replication strategies of marburg virus and Ebola virus by using artificial replication systems. J Virol 73(3):2333–2342

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nanbo A, Imai M, Watanabe S, Noda T, Takahashi K, Neumann G, Halfmann P, Kawaoka Y (2010) Ebolavirus is internalized into host cells via macropinocytosis in a viral glycoprotein-dependent manner. PLoS Pathog 6(9):e1001121. doi:10.1371/journal.ppat.1001121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nanbo A, Watanabe S, Halfmann P, Kawaoka Y (2013) The spatio-temporal distribution dynamics of Ebola virus proteins and RNA in infected cells. Scientific reports 3:1206. doi:10.1038/srep01206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nanclares C, Kapetshi J, Lionetto F, de la Rosa O, Tamfun JJ, Alia M, Kobinger G, Bernasconi A (2016) Ebola Virus Disease, Democratic Republic of the Congo, 2014. Emerg Infect Dis 22(9):1579–1586. doi:10.3201/eid2209.160354

    Article  PubMed  PubMed Central  Google Scholar 

  • Natesan M, Jensen SM, Keasey SL, Kamata T, Kuehne AI, Stonier SW, Lutwama JJ, Lobel L, Dye JM, Ulrich RG (2016) Human survivors of disease outbreaks caused by Ebola or marburg virus exhibit cross-reactive and long-lived antibody responses. Clin Vaccine Immunol 23(8):717–724. doi:10.1128/CVI.00107-16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ndungo E, Herbert AS, Raaben M, Obernosterer G, Biswas R, Miller EH, Wirchnianski AS, Carette JE, Brummelkamp TR, Whelan SP, Dye JM, Chandran K (2016) A single residue in ebola virus receptor npc1 influences cellular host range in reptiles. mSphere 1 (2). doi:10.1128/mSphere.00007-16

  • Nelson EV, Schmidt KM, Deflube LR, Doganay S, Banadyga L, Olejnik J, Hume AJ, Ryabchikova E, Ebihara H, Kedersha N, Ha T, Muhlberger E (2016) Ebola virus does not induce stress granule formation during infection and sequesters stress granule proteins within viral inclusions. J Virol 90(16):7268–7284. doi:10.1128/JVI.00459-16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neumann G, Watanabe S, Kawaoka Y (2009) Characterization of Ebolavirus regulatory genomic regions. Virus Res 144(1–2):1–7. doi:10.1016/j.virusres.2009.02.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ng M, Ndungo E, Jangra RK, Cai Y, Postnikova E, Radoshitzky SR, Dye JM, Ramirez de Arellano E, Negredo A, Palacios G, Kuhn JH, Chandran K (2014) Cell entry by a novel European filovirus requires host endosomal cysteine proteases and Niemann-Pick C1. Virology 468–470:637–646. doi:10.1016/j.virol.2014.08.019

    Article  CAS  PubMed  Google Scholar 

  • Ng M, Ndungo E, Kaczmarek ME, Herbert AS, Binger T, Kuehne AI, Jangra RK, Hawkins JA, Gifford RJ, Biswas R, Demogines A, James RM, Yu M, Brummelkamp TR, Drosten C, Wang LF, Kuhn JH, Muller MA, Dye JM, Sawyer SL, Chandran K (2015) Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats. Elife 4. doi:10.7554/eLife.11785

  • Ni M, Chen C, Qian J, Xiao HX, Shi WF, Luo Y, Wang HY, Li Z, Wu J, Xu PS, Chen SH, Wong G, Bi Y, Xia ZP, Li W, Lu HJ, Ma J, Tong YG, Zeng H, Wang SQ, Gao GF, Bo XC, Liu D (2016) Intra-host dynamics of Ebola virus during 2014. Nat Microbiol 1(11):16151. doi:10.1038/nmicrobiol.2016.151

    Article  CAS  PubMed  Google Scholar 

  • Noda T, Kolesnikova L, Becker S, Kawaoka Y (2011) The importance of the NP: VP35 ratio in Ebola virus nucleocapsid formation. J Infect Dis 204(Suppl 3):S878–S883. doi:10.1093/infdis/jir310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Noyori O, Matsuno K, Kajihara M, Nakayama E, Igarashi M, Kuroda M, Isoda N, Yoshida R, Takada A (2013) Differential potential for envelope glycoprotein-mediated steric shielding of host cell surface proteins among filoviruses. Virology 446(1–2):152–161. doi:10.1016/j.virol.2013.07.029

    Article  CAS  PubMed  Google Scholar 

  • O’Hearn A, Wang M, Cheng H, Lear-Rooney CM, Koning K, Rumschlag-Booms E, Varhegyi E, Olinger G, Rong L (2015) Role of EXT1 and glycosaminoglycans in the early stage of filovirus entry. J Virol 89(10):5441–5449. doi:10.1128/JVI.03689-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ohuabunwo C, Ameh C, Oduyebo O, Ahumibe A, Mutiu B, Olayinka A, Gbadamosi W, Garcia E, Nanclares C, Famiyesin W, Mohammed A, Nguku P, Koko RI, Obasanya J, Adebayo D, Gbadegesin Y, Idigbe O, Oguntimehin O, Nyanti S, Nzuki C, Abdus-Salam I, Adeyemi J, Onyekwere N, Musa E, Brett-Major D, Shuaib F, Nasidi A (2016) Clinical profile and containment of the Ebola virus disease outbreak in two large West African cities, Nigeria, July-September 2014. Int J Infect Dis. doi:10.1016/j.ijid.2016.08.011

    Article  PubMed  Google Scholar 

  • Okumura A, Pitha PM, Harty RN (2008) ISG15 inhibits Ebola VP40 VLP budding in an L-domain-dependent manner by blocking Nedd4 ligase activity. Proc Natl Acad Sci USA 105(10):3974–3979. doi:10.1073/pnas.0710629105

    Article  PubMed  Google Scholar 

  • 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(1):27–33. doi:10.1128/JVI.01462-09

    Article  CAS  PubMed  Google Scholar 

  • Okumura A, Rasmussen AL, Halfmann P, Feldmann F, Yoshimura A, Feldmann H, Kawaoka Y, Harty RN, Katze MG (2015) Suppressor of cytokine signaling 3 is an inducible host factor that regulates virus egress during ebola virus infection. J Virol 89(20):10399–10406. doi:10.1128/JVI.01736-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Olsen ME, Filone CM, Rozelle D, Mire CE, Agans KN, Hensley L, Connor JH (2016) Polyamines and hypusination are required for ebolavirus gene expression and replication. mBio 7(4). doi:10.1128/mBio.00882-16

  • O’Shea MK, Clay KA, Craig DG, Moore AJ, Lewis S, Espina M, Praught J, Horne S, Kao R, Johnston AM (2016) A health care worker with ebola virus disease and adverse prognostic factors treated in sierra leone. Am J Trop Med Hyg 94(4):829–832. doi:10.4269/ajtmh.15-0461

    Article  PubMed  PubMed Central  Google Scholar 

  • 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 USA 100(26):15936–15941. doi:10.1073/pnas.2533915100

    Article  CAS  PubMed  Google Scholar 

  • Panchal RG, Bradfute SB, Peyser B, Warfield KL, Ruthel G, Lane D, Kenny TA, Anderson AO, Raschke WC, Bavari S (2009) Reduced levels of protein tyrosine phosphatase CD45 protect mice from the lethal effects of Ebola virus infection. Cell Host Microbe 6(2):162–173. doi:10.1016/j.chom.2009.07.003

    Article  CAS  PubMed  Google Scholar 

  • Perry DL, Bollinger L, White GL (2012) The Baboon (Papio spp.) as a model of human Ebola virus infection. Viruses 4(10):2400–2416. doi:10.3390/v4102400

    Article  PubMed  PubMed Central  Google Scholar 

  • Peyrol J, Thizon C, Gaillard JC, Marchetti C, Armengaud J, Rollin-Genetet F (2013) Multiple phosphorylable sites in the Zaire Ebolavirus nucleoprotein evidenced by high resolution tandem mass spectrometry. J Virol Methods 187(1):159–165. doi:10.1016/j.jviromet.2012.10.003

    Article  CAS  PubMed  Google Scholar 

  • Powlesland AS, Fisch T, Taylor ME, Smith DF, Tissot B, Dell A, Pohlmann S, Drickamer K (2008) A novel mechanism for LSECtin binding to Ebola virus surface glycoprotein through truncated glycans. J Biol Chem 283(1):593–602. doi:10.1074/jbc.M706292200

    Article  CAS  PubMed  Google Scholar 

  • Prescott J, Falzarano D, Feldmann H (2015) Natural immunity to ebola virus in the syrian hamster requires antibody responses. J Infect Dis 212(Suppl 2):S271–S276. doi:10.1093/infdis/jiv203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prins KC, Delpeut S, Leung DW, Reynard O, Volchkova VA, Reid SP, Ramanan P, Cardenas WB, Amarasinghe GK, Volchkov VE, Basler CF (2010) Mutations abrogating VP35 interaction with double-stranded RNA render Ebola virus avirulent in guinea pigs. J Virol 84(6):3004–3015. doi:10.1128/JVI.02459-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qin E, Bi J, Zhao M, Wang Y, Guo T, Yan T, Li Z, Sun J, Zhang J, Chen S, Wu Y, Li J, Zhong Y (2015) Clinical features of patients with ebola virus disease in Sierra Leone. Clin Infect Dis: An Official Publ Infect Dis Soc Am 61(4):491–495. doi:10.1093/cid/civ319

    Article  Google Scholar 

  • Quinn K, Brindley MA, Weller ML, Kaludov N, Kondratowicz A, Hunt CL, Sinn PL, McCray PB Jr, Stein CS, Davidson BL, Flick R, Mandell R, Staplin W, Maury W, Chiorini JA (2009) Rho GTPases modulate entry of Ebola virus and vesicular stomatitis virus pseudotyped vectors. J Virol 83(19):10176–10186. doi:10.1128/JVI.00422-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramaiah A, Arumugaswami V (2016) Ebolavirus evolves in human to minimize the detection by immune cells by accumulating adaptive mutations. Virusdisease 27(2):136–144. doi:10.1007/s13337-016-0305-0

    Article  PubMed  PubMed Central  Google Scholar 

  • Rasmussen AL, Okumura A, Ferris MT, Green R, Feldmann F, Kelly SM, Scott DP, Safronetz D, Haddock E, LaCasse R, Thomas MJ, Sova P, Carter VS, Weiss JM, Miller DR, Shaw GD, Korth MJ, Heise MT, Baric RS, de Villena FP, Feldmann H, Katze MG (2014) Host genetic diversity enables Ebola hemorrhagic fever pathogenesis and resistance. Science 346(6212):987–991. doi:10.1126/science.1259595

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reed DS, Hensley LE, Geisbert JB, Jahrling PB, Geisbert TW (2004) Depletion of peripheral blood T lymphocytes and NK cells during the course of ebola hemorrhagic Fever in cynomolgus macaques. Viral Immunol 17(3):390–400. doi:10.1089/vim.2004.17.390

    Article  CAS  PubMed  Google Scholar 

  • Reid SP, Leung LW, Hartman AL, Martinez O, Shaw ML, Carbonnelle C, Volchkov VE, Nichol ST, Basler CF (2006) Ebola virus VP24 binds karyopherin alpha1 and blocks STAT1 nuclear accumulation. J Virol 80(11):5156–5167. doi:10.1128/JVI.02349-05

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reid SP, Valmas C, Martinez O, Sanchez FM, Basler CF (2007) Ebola virus VP24 proteins inhibit the interaction of NPI-1 subfamily karyopherin alpha proteins with activated STAT1. J Virol 81(24):13469–13477. doi:10.1128/JVI.01097-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reid SP, Shurtleff AC, Costantino JA, Tritsch SR, Retterer C, Spurgers KB, Bavari S (2014) HSPA5 is an essential host factor for Ebola virus infection. Antiviral Res 109:171–174. doi:10.1016/j.antiviral.2014.07.004

    Article  CAS  PubMed  Google Scholar 

  • Reynard O, Volchkov VE (2015) Entry of Ebola virus is an asynchronous process. J Infect Dis 212(Suppl 2):S199–S203. doi:10.1093/infdis/jiv189

    Article  CAS  PubMed  Google Scholar 

  • 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(18):9596–9601. doi:10.1128/JVI.00784-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reynard O, Nemirov K, Page A, Mateo M, Raoul H, Weissenhorn W, Volchkov VE (2011) Conserved proline-rich region of Ebola virus matrix protein VP40 is essential for plasma membrane targeting and virus-like particle release. J Infect Dis 204(Suppl 3):S884–S891. doi:10.1093/infdis/jir359

    Article  CAS  PubMed  Google Scholar 

  • Rhein BA, Brouillette RB, Schaack GA, Chiorini JA, Maury W (2016) Characterization of human and murine T-cell immunoglobulin mucin domain 4 (TIM-4) IgV domain residues critical for Ebola virus entry. J Virol 90(13):6097–6111. doi:10.1128/JVI.00100-16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rialdi A, Campisi L, Zhao N, Lagda AC, Pietzsch C, Ho JS, Martinez-Gil L, Fenouil R, Chen X, Edwards M, Metreveli G, Jordan S, Peralta Z, Munoz-Fontela C, Bouvier N, Merad M, Jin J, Weirauch M, Heinz S, Benner C, van Bakel H, Basler C, Garcia-Sastre A, Bukreyev A, Marazzi I (2016) Topoisomerase inhibition suppresses inflammatory genes and protects from death by inflammation. Science 352(6289):aad7993. doi:10.1126/science.aad7993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Richard AS, Zhang A, Park SJ, Farzan M, Zong M, Choe H (2015) Virion-associated phosphatidylethanolamine promotes TIM1-mediated infection by Ebola, dengue, and West Nile viruses. Proc Natl Acad Sci USA 112(47):14682–14687. doi:10.1073/pnas.1508095112

    Article  CAS  PubMed  Google Scholar 

  • Roddy P, Howard N, Van Kerkhove MD, Lutwama J, Wamala J, Yoti Z, Colebunders R, Palma PP, Sterk E, Jeffs B, Van Herp M, Borchert M (2012) Clinical manifestations and case management of Ebola haemorrhagic fever caused by a newly identified virus strain, Bundibugyo, Uganda, 2007–2008. PLoS ONE 7(12):e52986. doi:10.1371/journal.pone.0052986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rubins KH, Hensley LE, Wahl-Jensen V, Daddario DiCaprio KM, Young HA, Reed DS, Jahrling PB, Brown PO, Relman DA, Geisbert TW (2007) The temporal program of peripheral blood gene expression in the response of nonhuman primates to Ebola hemorrhagic fever. Genome Biol 8(8):R174. doi:10.1186/gb-2007-8-8-r174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ryabchikova EI, Kolesnikova LV, Luchko SV (1999) An analysis of features of pathogenesis in two animal models of Ebola virus infection. J Infect Dis 179(Suppl 1):S199–S202. doi:10.1086/514293

    Article  PubMed  Google Scholar 

  • Saeed MF, Kolokoltsov AA, Freiberg AN, Holbrook MR, Davey RA (2008) Phosphoinositide-3 kinase-Akt pathway controls cellular entry of Ebola virus. PLoS Pathog 4(8):e1000141. doi:10.1371/journal.ppat.1000141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saeed MF, Kolokoltsov AA, Albrecht T, Davey RA (2010) Cellular entry of ebola virus involves uptake by a macropinocytosis-like mechanism and subsequent trafficking through early and late endosomes. PLoS Pathog 6(9):e1001110. doi:10.1371/journal.ppat.1001110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sakurai Y, Kolokoltsov AA, Chen CC, Tidwell MW, Bauta WE, Klugbauer N, Grimm C, Wahl-Schott C, Biel M, Davey RA (2015) Ebola virus. Two-pore channels control Ebola virus host cell entry and are drug targets for disease treatment. Science 347(6225):995–998. doi:10.1126/science.1258758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salvador B, Sexton NR, Carrion R Jr, Nunneley J, Patterson JL, Steffen I, Lu K, Muench MO, Lembo D, Simmons G (2013) Filoviruses utilize glycosaminoglycans for their attachment to target cells. J Virol 87(6):3295–3304. doi:10.1128/JVI.01621-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 USA 93(8):3602–3607

    Article  CAS  Google Scholar 

  • Sanchez A, Lukwiya M, Bausch D, Mahanty S, Sanchez AJ, Wagoner KD, Rollin PE (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(19):10370–10377. doi:10.1128/JVI.78.19.10370-10377.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sanchez A, Geisbert TW, Feldmann H (2007) Filoviridae: Marburg and Ebola viruses. In: Knipe DM, Howley PM (eds) Fields Virology, 5th edn. Lippincott Williams & Wilkins, Philadelphia, pp 1409–1448 (Vol. 1)

    Google Scholar 

  • Schibler M, Vetter P, Cherpillod P, Petty TJ, Cordey S, Vieille G, Yerly S, Siegrist CA, Samii K, Dayer JA, Docquier M, Zdobnov EM, Simpson AJ, Rees PS, Sarria FB, Gasche Y, Chappuis F, Iten A, Pittet D, Pugin J, Kaiser L (2015) Clinical features and viral kinetics in a rapidly cured patient with Ebola virus disease: a case report. Lancet Infect Dis 15(9):1034–1040. doi:10.1016/S1473-3099(15)00229-7

    Article  PubMed  Google Scholar 

  • Schieffelin JS, Shaffer JG, Goba A, Gbakie M, Gire SK, Colubri A, Sealfon RS, Kanneh L, Moigboi A, Momoh M, Fullah M, Moses LM, Brown BL, Andersen KG, Winnicki S, Schaffner SF, Park DJ, Yozwiak NL, Jiang PP, Kargbo D, Jalloh S, Fonnie M, Sinnah V, French I, Kovoma A, Kamara FK, Tucker V, Konuwa E, Sellu J, Mustapha I, Foday M, Yillah M, Kanneh F, Saffa S, Massally JL, Boisen ML, Branco LM, Vandi MA, Grant DS, Happi C, Gevao SM, Fletcher TE, Fowler RA, Bausch DG, Sabeti PC, Khan SH, Garry RF, Program KGHLF, Viral Hemorrhagic Fever C, Team WHOCR (2014) Clinical illness and outcomes in patients with Ebola in Sierra Leone. The New England journal of medicine 371(22):2092–2100. doi:10.1056/NEJMoa1411680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schornberg K, Matsuyama S, Kabsch K, Delos S, Bouton A, White J (2006) Role of endosomal cathepsins in entry mediated by the Ebola virus glycoprotein. J Virol 80(8):4174–4178. doi:10.1128/JVI.80.8.4174-4178.2006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schornberg KL, Shoemaker CJ, Dube D, Abshire MY, Delos SE, Bouton AH, White JM (2009) Alpha5beta1-integrin controls ebolavirus entry by regulating endosomal cathepsins. Proc Natl Acad Sci USA 106(19):8003–8008. doi:10.1073/pnas.0807578106

    Article  CAS  PubMed  Google Scholar 

  • Schudt G, Dolnik O, Kolesnikova L, Biedenkopf N, Herwig A, Becker S (2015) Transport of ebolavirus nucleocapsids is dependent on actin polymerization: live-cell imaging analysis of ebolavirus-infected cells. J Infect Dis 212(Suppl 2):S160–S166. doi:10.1093/infdis/jiv083

    Article  CAS  PubMed  Google Scholar 

  • Schumann M, Gantke T, Muhlberger E (2009) Ebola virus VP35 antagonizes PKR activity through its C-terminal interferon inhibitory domain. J Virol 83(17):8993–8997. doi:10.1128/JVI.00523-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shabman RS, Gulcicek EE, Stone KL, Basler CF (2011a) The Ebola virus VP24 protein prevents hnRNP C1/C2 binding to karyopherin alpha1 and partially alters its nuclear import. J Infect Dis 204(Suppl 3):S904–S910. doi:10.1093/infdis/jir323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shabman RS, Leung DW, Johnson J, Glennon N, Gulcicek EE, Stone KL, Leung L, Hensley L, Amarasinghe GK, Basler CF (2011b) DRBP76 associates with Ebola virus VP35 and suppresses viral polymerase function. J Infect Dis 204(Suppl 3):S911–S918. doi:10.1093/infdis/jir343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shabman RS, Hoenen T, Groseth A, Jabado O, Binning JM, Amarasinghe GK, Feldmann H, Basler CF (2013) An upstream open reading frame modulates ebola virus polymerase translation and virus replication. PLoS Pathog 9(1):e1003147. doi:10.1371/journal.ppat.1003147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shabman RS, Jabado OJ, Mire CE, Stockwell TB, Edwards M, Mahajan M, Geisbert TW, Basler CF (2014) Deep sequencing identifies noncanonical editing of Ebola and Marburg virus RNAs in infected cells. mBio 5(6):e02011. doi:10.1128/mBio.02011-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shimojima M, Takada A, Ebihara H, Neumann G, Fujioka K, Irimura T, Jones S, Feldmann H, Kawaoka Y (2006) Tyro3 family-mediated cell entry of Ebola and Marburg viruses. J Virol 80(20):10109–10116. doi:10.1128/JVI.01157-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shimojima M, Ikeda Y, Kawaoka Y (2007) The mechanism of Axl-mediated Ebola virus infection. J Infect Dis 196(Suppl 2):S259–S263. doi:10.1086/520594

    Article  CAS  PubMed  Google Scholar 

  • Silvestri LS, Ruthel G, Kallstrom G, Warfield KL, Swenson DL, Nelle T, Iversen PL, Bavari S, Aman MJ (2007) Involvement of vacuolar protein sorting pathway in Ebola virus release independent of TSG101 interaction. J Infect Dis 196(Suppl 2):S264–S270. doi:10.1086/520610

    Article  CAS  PubMed  Google Scholar 

  • Simmons G, Reeves JD, Grogan CC, Vandenberghe LH, Baribaud F, Whitbeck JC, Burke E, Buchmeier MJ, Soilleux EJ, Riley JL, Doms RW, Bates P, Pohlmann S (2003a) DC-SIGN and DC-SIGNR bind ebola glycoproteins and enhance infection of macrophages and endothelial cells. Virology 305(1):115–123

    Article  CAS  Google Scholar 

  • Simmons G, Rennekamp AJ, Chai N, Vandenberghe LH, Riley JL, Bates P (2003b) Folate receptor alpha and caveolae are not required for Ebola virus glycoprotein-mediated viral infection. J Virol 77(24):13433–13438

    Article  CAS  Google Scholar 

  • Smith DR, McCarthy S, Chrovian A, Olinger G, Stossel A, Geisbert TW, Hensley LE, Connor JH (2010) Inhibition of heat-shock protein 90 reduces Ebola virus replication. Antiviral Res 87(2):187–194. doi:10.1016/j.antiviral.2010.04.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sobarzo A, Groseth A, Dolnik O, Becker S, Lutwama JJ, Perelman E, Yavelsky V, Muhammad M, Kuehne AI, Marks RS, Dye JM, Lobel L (2013) Profile and persistence of the virus-specific neutralizing humoral immune response in human survivors of Sudan ebolavirus (Gulu). J Infect Dis 208(2):299–309. doi:10.1093/infdis/jit162

    Article  CAS  PubMed  Google Scholar 

  • Soni SP, Stahelin RV (2014) The Ebola virus matrix protein VP40 selectively induces vesiculation from phosphatidylserine-enriched membranes. J Biol Chem 289(48):33590–33597. doi:10.1074/jbc.M114.586396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soni SP, Adu-Gyamfi E, Yong SS, Jee CS, Stahelin RV (2013) The Ebola virus matrix protein deeply penetrates the plasma membrane: an important step in viral egress. Biophys J 104(9):1940–1949. doi:10.1016/j.bpj.2013.03.021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Spence JS, Krause TB, Mittler E, Jangra RK, Chandran K (2016) Direct visualization of Ebola virus fusion triggering in the endocytic pathway. mBio 7(1):e01857–e01815. doi:10.1128/mBio.01857-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Spengler JR, Lavender KJ, Martellaro C, Carmody A, Kurth A, Keck JG, Saturday G, Scott DP, Nichol ST, Hasenkrug KJ, Spiropoulou CF, Feldmann H, Prescott J (2016) Ebola virus replication and disease without immunopathology in mice expressing transgenes to support human Myeloid and Lymphoid cell engraftment. J Infect Dis 214(suppl 3):S308–S318. doi:10.1093/infdis/jiw248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Spurgers KB, Alefantis T, Peyser BD, Ruthel GT, Bergeron AA, Costantino JA, Enterlein S, Kota KP, Boltz RC, Aman MJ, Delvecchio VG, Bavari S (2010) Identification of essential filovirion-associated host factors by serial proteomic analysis and RNAi screen. Mol Cell Proteomics 9(12):2690–2703. doi:10.1074/mcp.M110.003418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Strong JE, Wong G, Jones SE, Grolla A, Theriault S, Kobinger GP, Feldmann H (2008) Stimulation of Ebola virus production from persistent infection through activation of the Ras/MAPK pathway. Proc Natl Acad Sci USA 105(46):17982–17987. doi:10.1073/pnas.0809698105

    Article  PubMed  Google Scholar 

  • Sztuba-Solinska J, Diaz L, Kumar MR, Kolb G, Wiley MR, Jozwick L, Kuhn JH, Palacios G, Radoshitzky SR, JLG SF, Johnson RF (2016) A small stem-loop structure of the Ebola virus trailer is essential for replication and interacts with heat-shock protein A8. Nucleic Acids Res. doi:10.1093/nar/gkw825

    Article  PubMed  PubMed Central  Google Scholar 

  • 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(1):20–26. doi:10.1006/viro.2000.0601

    Article  CAS  PubMed  Google Scholar 

  • Takada A, Fujioka K, Tsuiji M, Morikawa A, Higashi N, Ebihara H, Kobasa D, Feldmann H, Irimura T, Kawaoka Y (2004) Human macrophage C-type lectin specific for galactose and N-acetylgalactosamine promotes filovirus entry. J Virol 78(6):2943–2947

    Article  CAS  Google Scholar 

  • Takahashi K, Halfmann P, Oyama M, Kozuka-Hata H, Noda T, Kawaoka Y (2013) DNA topoisomerase 1 facilitates the transcription and replication of the Ebola virus genome. J Virol 87(16):8862–8869. doi:10.1128/JVI.03544-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Timmins J, Schoehn G, Ricard-Blum S, Scianimanico S, Vernet T, Ruigrok RW, Weissenhorn W (2003) Ebola virus matrix protein VP40 interaction with human cellular factors Tsg101 and Nedd4. J Mol Biol 326(2):493–502

    Article  CAS  Google Scholar 

  • Usami K, Matsuno K, Igarashi M, Denda-Nagai K, Takada A, Irimura T (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(1):74–78. doi:10.1016/j.bbrc.2011.02.110

    Article  CAS  PubMed  Google Scholar 

  • Uyeki TM, Mehta AK, Davey RT, Jr., Liddell AM, Wolf T, Vetter P, Schmiedel S, Grunewald T, Jacobs M, Arribas JR, Evans L, Hewlett AL, Brantsaeter AB, Ippolito G, Rapp C, Hoepelman AI, Gutman J, Working Group of the USECNoCMoEVDPitUS, Europe (2016) Clinical Management of Ebola Virus Disease in the United States and Europe. The New England journal of medicine 374 (7):636-646. doi:10.1056/NEJMoa1504874

    Article  CAS  Google Scholar 

  • Valmas C, Grosch MN, Schumann M, Olejnik J, Martinez O, Best SM, Krahling V, Basler CF, Muhlberger E (2010) Marburg virus evades interferon responses by a mechanism distinct from ebola virus. PLoS Pathog 6(1):e1000721. doi:10.1371/journal.ppat.1000721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vande Burgt NH, Kaletsky RL, Bates P (2015) Requirements within the Ebola Viral Glycoprotein for Tetherin Antagonism. Viruses 7(10):5587–5602. doi:10.3390/v7102888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(2):421–430

    Article  CAS  Google Scholar 

  • Volchkov VE, Feldmann H, Volchkova VA, Klenk HD (1998) Processing of the Ebola virus glycoprotein by the proprotein convertase furin. Proc Natl Acad Sci USA 95(10):5762–5767

    Article  CAS  Google Scholar 

  • Volchkova VA, Feldmann H, Klenk HD, Volchkov VE (1998) The nonstructural small glycoprotein sGP of Ebola virus is secreted as an antiparallel-orientated homodimer. Virology 250(2):408–414. doi:10.1006/viro.1998.9389

    Article  CAS  PubMed  Google Scholar 

  • 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(1):164–171. doi:10.1006/viro.1999.0034

    Article  CAS  PubMed  Google Scholar 

  • Volchkova VA, Dolnik O, Martinez MJ, Reynard O, Volchkov VE (2011) Genomic RNA editing and its impact on Ebola virus adaptation during serial passages in cell culture and infection of guinea pigs. J Infect Dis 204(Suppl 3):S941–S946. doi:10.1093/infdis/jir321

    Article  CAS  PubMed  Google Scholar 

  • Volchkova VA, Dolnik O, Martinez MJ, Reynard O, Volchkov VE (2015a) RNA editing of the GP gene of Ebola virus is an important pathogenicity factor. J Infect Dis 212(Suppl 2):S226–S233. doi:10.1093/infdis/jiv309

    Article  CAS  PubMed  Google Scholar 

  • Volchkova VA, Vorac J, Repiquet-Paire L, Lawrence P, Volchkov VE (2015b) Ebola virus GP gene polyadenylation versus RNA editing. J Infect Dis 212(Suppl 2):S191–S198. doi:10.1093/infdis/jiv150

    Article  CAS  PubMed  Google Scholar 

  • 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(4):2413–2419. doi:10.1128/JVI.79.4.2413-2419.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(16):10442–10450. doi:10.1128/JVI.79.16.10442-10450.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wahl-Jensen V, Kurz S, Feldmann F, Buehler LK, Kindrachuk J, DeFilippis V, da Silva Correia J, Fruh K, Kuhn JH, Burton DR, Feldmann H (2011) Ebola virion attachment and entry into human macrophages profoundly effects early cellular gene expression. PLoS neglected tropical diseases 5(10):e1359. doi:10.1371/journal.pntd.0001359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Watt A, Moukambi F, Banadyga L, Groseth A, Callison J, Herwig A, Ebihara H, Feldmann H, Hoenen T (2014) A novel life cycle modeling system for Ebola virus shows a genome length-dependent role of VP24 in virus infectivity. J Virol 88(18):10511–10524. doi:10.1128/JVI.01272-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wauquier N, Becquart P, Gasquet C, Leroy EM (2009) Immunoglobulin G in Ebola outbreak survivors. Gabon. Emerg Infect Dis 15(7):1136–1137. doi:10.3201/eid1507.090402

    Article  PubMed  Google Scholar 

  • Wauquier N, Becquart P, Padilla C, Baize S, Leroy EM (2010) Human fatal zaire ebola virus infection is associated with an aberrant innate immunity and with massive lymphocyte apoptosis. PLoS neglected tropical diseases 4 (10). doi:10.1371/journal.pntd.0000837

    Article  Google Scholar 

  • WHO (1978a) Ebola haemorrhagic fever in Sudan, 1976. Report of a WHO/International Study Team. Bull World Health Organ 56(2):247–270

    Google Scholar 

  • WHO (1978b) Ebola haemorrhagic fever in Zaire, 1976. Bull World Health Organ 56(2):271–293

    Google Scholar 

  • WHO (2014) Ebola virus disease in West Africa–the first 9 months of the epidemic and forward projections. The New England journal of medicine 371(16):1481–1495. doi:10.1056/NEJMoa1411100

    Article  CAS  Google Scholar 

  • WHO (2016) Situation Report-Ebola Virus Disease, 10 June 2016. World Health Organization, World Health Organization Situation Report

    Google Scholar 

  • Wolf T, Kann G, Becker S, Stephan C, Brodt HR, de Leuw P, Grunewald T, Vogl T, Kempf VA, Keppler OT, Zacharowski K (2015) Severe Ebola virus disease with vascular leakage and multiorgan failure: treatment of a patient in intensive care. Lancet 385(9976):1428–1435. doi:10.1016/S0140-6736(14)62384-9

    Article  PubMed  Google Scholar 

  • Wong AC, Sandesara RG, Mulherkar N, Whelan SP, Chandran K (2010) A forward genetic strategy reveals destabilizing mutations in the Ebolavirus glycoprotein that alter its protease dependence during cell entry. J Virol 84(1):163–175. doi:10.1128/JVI.01832-09

    Article  CAS  PubMed  Google Scholar 

  • Wong KK, Perdue CL, Malia J, Kenney JL, Peng S, Gwathney JK, Raczniak GA, Monrovia Medical U (2015) Supportive Care of the First 2 Ebola Virus Disease Patients at the Monrovia Medical Unit. Clin Infect Dis: an Official Publ Infect Dis Soc Am 61(7):e47–e51. doi:10.1093/cid/civ420

    Article  Google Scholar 

  • Wrensch F, Karsten CB, Gnirss K, Hoffmann M, Lu K, Takada A, Winkler M, Simmons G, Pohlmann S (2015) Interferon-induced transmembrane protein-mediated inhibition of host cell entry of ebolaviruses. J Infect Dis 212(Suppl 2):S210–S218. doi:10.1093/infdis/jiv255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu W, Edwards MR, Borek DM, Feagins AR, Mittal A, Alinger JB, Berry KN, Yen B, Hamilton J, Brett TJ, Pappu RV, Leung DW, Basler CF, Amarasinghe GK (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(2):187–200. doi:10.1016/j.chom.2014.07.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamayoshi S, Noda T, Ebihara H, Goto H, Morikawa Y, Lukashevich IS, Neumann G, Feldmann H, Kawaoka Y (2008) Ebola virus matrix protein VP40 uses the COPII transport system for its intracellular transport. Cell Host Microbe 3(3):168–177. doi:10.1016/j.chom.2008.02.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yasuda J, Nakao M, Kawaoka Y, Shida H (2003) Nedd4 regulates egress of Ebola virus-like particles from host cells. J Virol 77(18):9987–9992

    Article  CAS  Google Scholar 

  • Yen BC, Basler CF (2016) Effects of filovirus interferon antagonists on responses of human monocyte-derived dendritic cells to RNA virus infection. J Virol 90(10):5108–5118. doi:10.1128/JVI.00191-16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yen JY, Garamszegi S, Geisbert JB, Rubins KH, Geisbert TW, Honko A, Xia Y, Connor JH, Hensley LE (2011) Therapeutics of Ebola hemorrhagic fever: whole-genome transcriptional analysis of successful disease mitigation. J Infect Dis 204(Suppl 3):S1043–S1052. doi:10.1093/infdis/jir345

    Article  CAS  PubMed  Google Scholar 

  • Yen B, Mulder LC, Martinez O, Basler CF (2014) Molecular basis for ebolavirus VP35 suppression of human dendritic cell maturation. J Virol 88(21):12500–12510. doi:10.1128/JVI.02163-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yuan S, Cao L, Ling H, Dang M, Sun Y, Zhang X, Chen Y, Zhang L, Su D, Wang X, Rao Z (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. doi:10.1007/s13238-015-0220-y

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang AP, Bornholdt ZA, Liu T, Abelson DM, Lee DE, Li S, Woods VL Jr, Saphire EO (2012) The ebola virus interferon antagonist VP24 directly binds STAT1 and has a novel, pyramidal fold. PLoS Pathog 8(2):e1002550. doi:10.1371/journal.ppat.1002550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(3):e1005487. doi:10.1371/journal.ppat.1005487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zumbrun EE, Bloomfield HA, Dye JM, Hunter TC, Dabisch PA, Garza NL, Bramel NR, Baker RJ, Williams RD, Nichols DK, Nalca A (2012) A characterization of aerosolized Sudan virus infection in African green monkeys, cynomolgus macaques, and rhesus macaques. Viruses 4(10):2115–2136. doi:10.3390/v4102115

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Angela L. Rasmussen .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Rasmussen, A.L. (2017). Host Factors Involved in Ebola Virus Replication. In: Tripp, R., Tompkins, S. (eds) Roles of Host Gene and Non-coding RNA Expression in Virus Infection. Current Topics in Microbiology and Immunology, vol 419. Springer, Cham. https://doi.org/10.1007/82_2017_27

Download citation

Publish with us

Policies and ethics