Tackling Ebola: New insights into prophylactic and therapeutic intervention strategies

Genome Medicine

Volumn 3, Issue 1, 2011, Pages

  de Wit, Emmie ^a   Feldmann, Heinz ^a   Munster, Vincent J ^a  

^a NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVATED PROTEIN C; ANTISENSE OLIGONUCLEOTIDE; ANTIVIRUS AGENT; DNA VACCINE; EBOLA VACCINE; FGI 103; FGI 104; FGI 106; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; MATRIX PROTEIN; MESSENGER RNA; NUCLEOPROTEIN; UNCLASSIFIED DRUG; VIRUS GLYCOPROTEIN; VIRUS LIKE PARTICLE VACCINE; VIRUS NUCLEOPROTEIN; VIRUS PROTEIN; VIRUS PROTEIN 24; VIRUS PROTEIN 35; VIRUS VECTOR;

ADAPTIVE IMMUNITY; ADENOVIRUS 5; ANTISENSE THERAPY; ANTISENSE VECTOR; ANTIVIRAL ACTIVITY; ANTIVIRAL THERAPY; CROSS PROTECTION; DNA IMMUNIZATION; DNA VECTOR; EBOLA HEMORRHAGIC FEVER; EBOLA VIRUS; GOLD STANDARD; HIGH THROUGHPUT SCREENING; HUMAN; HUMORAL IMMUNITY; IMMUNE EVASION; IN VITRO STUDY; IN VIVO STUDY; INFECTION PREVENTION; INNATE IMMUNITY; NONHUMAN; PATHOGENICITY; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIMATE; PRIORITY JOURNAL; REVIEW; VESICULAR STOMATITIS VIRUS; VIRUS LIKE AGENT; VIRUS PATHOGENESIS; VIRUS RECOMBINANT; VIRUS REPLICATION; VIRUS VIRULENCE;

EID: 84555180548     PISSN: None     EISSN: 1756994X     Source Type: Journal    
DOI: 10.1186/gm219     Document Type: Review

References (97)

1. Feldmann H, Geisbert TW, Jahrling PB, Klenk HD, Netesov SV, Peters CJ, Sanchez A, Swanepoel R, Volchkov VE. Filoviridae. Virus Taxonomy: VIIIth Report of the International Committee on Taxonomy of Viruses 2005, 645-653. London: Elsevier/Academic Press, Fauquet C, Mayo MA, Maniloff J, Desselberger U, Ball LA.
2. Hayman DT, Emmerich P, Yu M, Wang LF, Suu-Ire R, Fooks AR, Cunningham AA, Wood JL. Long-term survival of an urban fruit bat seropositive for Ebola and Lagos bat viruses. Plos ONE 2010, 5:e11978. 10.1371/journal.pone.0011978, 2915915, 20694141.
3. Leroy EM, Kumulungui B, Pourrut X, Rouquet P, Hassanin A, Yaba P, Delicat A, Paweska JT, Gonzalez JP, Swanepoel R. Fruit bats as reservoirs of Ebola virus. Nature 2005, 438:575-576. 10.1038/438575a, 16319873.
4. Pourrut X, Delicat A, Rollin PE, Ksiazek TG, Gonzalez JP, Leroy EM. Spatial and temporal patterns of Zaire ebolavirus antibody prevalence in the possible reservoir bat species. J Infect Dis 2007, 196(Suppl 2):S176-S183. 10.1086/520541, 17940947.
5. Pourrut X, Souris M, Towner JS, Rollin PE, Nichol ST, Gonzalez JP, Leroy E. Large serological survey showing cocirculation of Ebola and Marburg viruses in Gabonese bat populations, and a high seroprevalence of both viruses in Rousettus aegyptiacus. BMC Infect Dis 2009, 9:159. 10.1186/1471-2334-9-159, 2761397, 19785757.
6. Ebola haemorrhagic fever in Zaire, 1976. Bull World Health Organ 1978, 56:271-293. 2395567, 307456.
7. Ebola haemorrhagic fever in Sudan, 1976. Report of a WHO/International Study Team. Bull World Health Organ 1978, 56:247-270. 2395561, 307455.
8. Sanchez A, Geisbert TW, Feldmann H. Filoviridae: Marburg and Ebola Viruses. Fields Virology 2007, 1409-1448. Philadelphia: Lippincott Williams & Wilkins, Knipe DM, Howley PM, 5.
9. Jahrling PB, Geisbert TW, Dalgard DW, Johnson ED, Ksiazek TG, Hall WC, Peters CJ. Preliminary report: isolation of Ebola virus from monkeys imported to USA. Lancet 1990, 335:502-505. 10.1016/0140-6736(90)90737-P, 1968529.
10. Barrette RW, Metwally SA, Rowland JM, Xu L, Zaki SR, Nichol ST, Rollin PE, Towner JS, Shieh WJ, Batten B, Sealy TK, Carrillo C, Moran KE, Bracht AJ, Mayr GA, Sirios-Cruz M, Catbagan DP, Lautner EA, Ksiazek TG, White WR, McIntosh MT. Discovery of swine as a host for the Reston ebolavirus. Science 2009, 325:204-206. 10.1126/science.1172705, 19590002.
11. Update: filovirus infections among persons with occupational exposure to nonhuman primates. MMWR Morb Mortal Wkly Rep 1990, 39:266-267. 273.
12. Miranda ME, White ME, Dayrit MM, Hayes CG, Ksiazek TG, Burans JP. Seroepidemiological study of filovirus related to Ebola in the Philippines. Lancet 1991, 337:425-426. 10.1016/0140-6736(91)91199-5, 1671441.
13. Le Guenno B, Formenty P, Wyers M, Gounon P, Walker F, Boesch C. Isolation and partial characterisation of a new strain of Ebola virus. Lancet 1995, 345:1271-1274. 10.1016/S0140-6736(95)90925-7, 7746057.
14. Towner JS, Sealy TK, Khristova ML, Albarino CG, Conlan S, Reeder SA, Quan PL, Lipkin WI, Downing R, Tappero JW, Okware S, Lutwama J, Bakamutumaho B, Kayiwa J, Comer JA, Rollin PE, Ksiazek TG, Nichol ST. Newly discovered ebola virus associated with hemorrhagic fever outbreak in Uganda. PLoS Pathog 2008, 4:e1000212. 10.1371/journal.ppat.1000212, 2581435, 19023410.
15. Formenty P, Boesch C, Wyers M, Steiner C, Donati F, Dind F, Walker F, Le Guenno B. Ebola virus outbreak among wild chimpanzees living in a rain forest of Cote d'Ivoire. J Infect Dis 1999, 179(Suppl 1):S120-S126. 10.1086/514296, 9988175.
16. Leroy EM, Rouquet P, Formenty P, Souquiere S, Kilbourne A, Froment JM, Bermejo M, Smit S, Karesh W, Swanepoel R, Zaki SR, Rollin PE. Multiple Ebola virus transmission events and rapid decline of central African wildlife. Science 2004, 303:387-390. 10.1126/science.1092528, 14726594.
17. Rouquet P, Froment JM, Bermejo M, Kilbourn A, Karesh W, Reed P, Kumulungui B, Yaba P, Delicat A, Rollin PE, Leroy EM. Wild animal mortality monitoring and human Ebola outbreaks, Gabon and Republic of Congo, 2001-2003. Emerg Infect Dis 2005, 11:283-290.
18. 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. Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo: clinical observations in 103 patients. J Infect Dis 1999, 179(Suppl 1):S1-S7. 10.1086/514308, 9988155.
19. Baize S, Leroy EM, Georges-Courbot MC, Capron M, Lansoud-Soukate J, Debre P, Fisher-Hoch SP, McCormick JB, Georges AJ. Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in Ebola virus-infected patients. Nat Med 1999, 5:423-426. 10.1038/7422, 10202932.
20. Villinger F, Rollin PE, Brar SS, Chikkala NF, Winter J, Sundstrom JB, Zaki SR, Swanepoel R, Ansari AA, Peters CJ. Markedly elevated levels of interferon (IFN)-gamma, IFN-alpha, interleukin (IL)-2, IL-10, and tumor necrosis factor-alpha associated with fatal Ebola virus infection. J Infect Dis 1999, 179(Suppl 1):S188-S191. 10.1086/514283, 9988183.
21. Wauquier N, Becquart P, Padilla C, Baize S, Leroy EM. Human fatal zaire ebola virus infection is associated with an aberrant innate immunity and with massive lymphocyte apoptosis. PLoS Negl Trop Dis 2010, 4:e837. 10.1371/journal.pntd.0000837, 2950153, 20957152.
22. Wahl-Jensen VM, Afanasieva TA, Seebach J, Stroher U, Feldmann H, Schnittler HJ. Effects of Ebola virus glycoproteins on endothelial cell activation and barrier function. J Virol 2005, 79:10442-10450. 10.1128/JVI.79.16.10442-10450.2005, 1182673, 16051836.
23. Geisbert TW, Young HA, Jahrling PB, Davis KJ, Kagan E, Hensley LE. Mechanisms underlying coagulation abnormalities in ebola hemorrhagic fever: overexpression of tissue factor in primate monocytes/macrophages is a key event. J Infect Dis 2003, 188:1618-1629. 10.1086/379724, 14639531.
24. Francica JR, Varela-Rohena A, Medvec A, Plesa G, Riley JL, Bates P. Steric shielding of surface epitopes and impaired immune recognition induced by the ebola virus glycoprotein. PLoS Pathog 2010, 6:e1001098. 10.1371/journal.ppat.1001098, 2936550, 20844579.
25. Reynard O, Borowiak M, Volchkova VA, Delpeut S, Mateo M, Volchkov VE. Ebolavirus glycoprotein GP masks both its own epitopes and the presence of cellular surface proteins. J Virol 2009, 83:9596-9601. 10.1128/JVI.00784-09, 2738224, 19587051.
26. Yaddanapudi K, Palacios G, Towner JS, Chen I, Sariol CA, Nichol ST, Lipkin WI. Implication of a retrovirus-like glycoprotein peptide in the immunopathogenesis of Ebola and Marburg viruses. FASEB J 2006, 20:2519-2530. 10.1096/fj.06-6151com, 17023517.
27. Okumura A, Pitha PM, Yoshimura A, Harty RN. Interaction between Ebola virus glycoprotein and host toll-like receptor 4 leads to induction of proinflammatory cytokines and SOCS1. J Virol 2010, 84:27-33. 10.1128/JVI.01462-09, 2798428, 19846529.
28. Kaletsky RL, Francica JR, Agrawal-Gamse C, Bates P. Tetherin-mediated restriction of filovirus budding is antagonized by the Ebola glycoprotein. Proc Natl Acad Sci USA 2009, 106:2886-2891. 10.1073/pnas.0811014106, 2650360, 19179289.
29. Ebihara H, Takada A, Kobasa D, Jones S, Neumann G, Theriault S, Bray M, Feldmann H, Kawaoka Y. Molecular determinants of Ebola virus virulence in mice. PLoS Pathog 2006, 2:e73. 10.1371/journal.ppat.0020073, 1513261, 16848640.
30. Volchkov VE, Chepurnov AA, Volchkova VA, Ternovoj VA, Klenk HD. Molecular characterization of guinea pig-adapted variants of Ebola virus. Virology 2000, 277:147-155. 10.1006/viro.2000.0572, 11062045.
31. Reid SP, Leung LW, Hartman AL, Martinez O, Shaw ML, Carbonnelle C, Volchkov VE, Nichol ST, Basler CF. Ebola virus VP24 binds karyopherin alpha1 and blocks STAT1 nuclear accumulation. J Virol 2006, 80:5156-5167. 10.1128/JVI.02349-05, 1472181, 16698996.
32. Mateo M, Reid SP, Leung LW, Basler CF, Volchkov VE. Ebolavirus VP24 binding to karyopherins is required for inhibition of interferon signaling. J Virol 2010, 84:1169-1175. 10.1128/JVI.01372-09, 2798383, 19889762.
33. Basler CF, Wang X, Muhlberger E, Volchkov V, Paragas J, Klenk HD, Garcia-Sastre A, Palese P. The Ebola virus VP35 protein functions as a type I IFN antagonist. Proc Natl Acad Sci USA 2000, 97:12289-12294. 10.1073/pnas.220398297, 17334, 11027311.
34. Basler CF, Mikulasova A, Martinez-Sobrido L, Paragas J, Muhlberger E, Bray M, Klenk HD, Palese P, Garcia-Sastre A. The Ebola virus VP35 protein inhibits activation of interferon regulatory factor 3. J Virol 2003, 77:7945-7956. 10.1128/JVI.77.14.7945-7956.2003, 161945, 12829834.
35. Cardenas WB, Loo YM, Gale M, Hartman AL, Kimberlin CR, Martinez-Sobrido L, Saphire EO, Basler CF. Ebola virus VP35 protein binds double-stranded RNA and inhibits alpha/beta interferon production induced by RIG-I signaling. J Virol 2006, 80:5168-5178. 10.1128/JVI.02199-05, 1472134, 16698997.
36. Hartman AL, Towner JS, Nichol ST. A C-terminal basic amino acid motif of Zaire ebolavirus VP35 is essential for type I interferon antagonism and displays high identity with the RNA-binding domain of another interferon antagonist, the NS1 protein of influenza A virus. Virology 2004, 328:177-184. 10.1016/j.virol.2004.07.006, 15464838.
37. Prins KC, Cardenas WB, Basler CF. Ebola virus protein VP35 impairs the function of interferon regulatory factor-activating kinases IKKepsilon and TBK-1. J Virol 2009, 83:3069-3077. 10.1128/JVI.01875-08, 2655579, 19153231.
38. Chang TH, Kubota T, Matsuoka M, Jones S, Bradfute SB, Bray M, Ozato K. Ebola Zaire virus blocks type I interferon production by exploiting the host SUMO modification machinery. PLoS Pathog 2009, 5:e1000493. 10.1371/journal.ppat.1000493, 2696038, 19557165.
39. Feng Z, Cerveny M, Yan Z, He B. The VP35 protein of Ebola virus inhibits the antiviral effect mediated by double-stranded RNA-dependent protein kinase PKR. J Virol 2007, 81:182-192. 10.1128/JVI.01006-06, 1797262, 17065211.
40. Schumann M, Gantke T, Muhlberger E. Ebola virus VP35 antagonizes PKR activity through its C-terminal interferon inhibitory domain. J Virol 2009, 83:8993-8997. 10.1128/JVI.00523-09, 2738155, 19515768.
41. Haasnoot J, de Vries W, Geutjes EJ, Prins M, de Haan P, Berkhout B. The Ebola virus VP35 protein is a suppressor of RNA silencing. PLoS Pathog 2007, 3:e86. 10.1371/journal.ppat.0030086, 1894824, 17590081.
42. Prins KC, Delpeut S, Leung DW, Reynard O, Volchkova VA, Reid SP, Ramanan P, Cardenas WB, Amarasinghe GK, Volchkov VE, Basler CF. Mutations abrogating VP35 interaction with double-stranded RNA render ebola virus avirulent in guinea pigs. J Virol 2010, 84:3004-3015. 10.1128/JVI.02459-09, 2826052, 20071589.
43. Jin H, Yan Z, Prabhakar BS, Feng Z, Ma Y, Verpooten D, Ganesh B, He B. The VP35 protein of Ebola virus impairs dendritic cell maturation induced by virus and lipopolysaccharide. J Gen Virol 2010, 91:352-361. 10.1099/vir.0.017343-0, 19828757.
44. Kash JC, Muhlberger E, Carter V, Grosch M, Perwitasari O, Proll SC, Thomas MJ, Weber F, Klenk HD, Katze MG. 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 2006, 80:3009-3020. 10.1128/JVI.80.6.3009-3020.2006, 1395418, 16501110.
45. Rubins KH, Hensley LE, Wahl-Jensen V, Daddario DiCaprio KM, Young HA, Reed DS, Jahrling PB, Brown PO, Relman DA, Geisbert TW. The temporal program of peripheral blood gene expression in the response of nonhuman primates to Ebola hemorrhagic fever. Genome Biol 2007, 8:R174. 10.1186/gb-2007-8-8-r174, 2375004, 17725815.
46. Quinn K, Brindley MA, Weller ML, Kaludov N, Kondratowicz A, Hunt CL, Sinn PL, McCray PB, Stein CS, Davidson BL, Flick R, Mandell R, Staplin W, Maury W, Chiorini JA. Rho GTPases modulate entry of Ebola virus and vesicular stomatitis virus pseudotyped vectors. J Virol 2009, 83:10176-10186. 10.1128/JVI.00422-09, 2747995, 19625394.
47. Smith DR, McCarthy S, Chrovian A, Olinger G, Stossel A, Geisbert TW, Hensley LE, Connor JH. Inhibition of heat-shock protein 90 reduces Ebola virus replication. Antiviral Res 2010, 87:187-194. 10.1016/j.antiviral.2010.04.015, 20452380.
48. Spurgers KB, Alefantis T, Peyser BD, Ruthel GT, Bergeron AA, Costantino JA, Enterlein S, Kota KP, Boltz RC, Aman MJ, Delvecchio VG, Bavari S. Identification of essential filovirion-associated host factors by serial proteomic analysis and RNAi screen. Mol Cell Proteomics 2010, 9:2690-2703. 10.1074/mcp.M110.003418, 20702783.
49. Geisbert TW, Pushko P, Anderson K, Smith J, Davis KJ, Jahrling PB. Evaluation in nonhuman primates of vaccines against Ebola virus. Emerg Infect Dis 2002, 8:503-507.
50. Lupton HW, Lambert RD, Bumgardner DL, Moe JB, Eddy GA. Inactivated vaccine for Ebola virus efficacious in guineapig model. Lancet 1980, 2:1294-1295. 10.1016/S0140-6736(80)92352-1, 6108462.
51. Rao M, Bray M, Alving CR, Jahrling P, Matyas GR. Induction of immune responses in mice and monkeys to Ebola virus after immunization with liposome-encapsulated irradiated Ebola virus: protection in mice requires CD4(+) T cells. J Virol 2002, 76:9176-9185. 10.1128/JVI.76.18.9176-9185.2002, 136452, 12186901.
52. Bente D, Gren J, Strong JE, Feldmann H. Disease modeling for Ebola and Marburg viruses. Dis Model Mech 2009, 2:12-17. 10.1242/dmm.000471, 2615158, 19132113.
53. Gupta M, Greer P, Mahanty S, Shieh WJ, Zaki SR, Ahmed R, Rollin PE. CD8-mediated protection against Ebola virus infection is perforin dependent. J Immunol 2005, 174:4198-4202.
54. Gupta M, Mahanty S, Greer P, Towner JS, Shieh WJ, Zaki SR, Ahmed R, Rollin PE. Persistent infection with ebola virus under conditions of partial immunity. J Virol 2004, 78:958-967. 10.1128/JVI.78.2.958-967.2004, 368745, 14694127.
55. Warfield KL, Olinger G, Deal EM, Swenson DL, Bailey M, Negley DL, Hart MK, Bavari S. Induction of humoral and CD8+ T cell responses are required for protection against lethal Ebola virus infection. J Immunol 2005, 175:1184-1191.
56. Warfield KL, Perkins JG, Swenson DL, Deal EM, Bosio CM, Aman MJ, Yokoyama WM, Young HA, Bavari S. Role of natural killer cells in innate protection against lethal ebola virus infection. J Exp Med 2004, 200:169-179. 10.1084/jem.20032141, 2212007, 15249592.
57. Hensley LE, Mulangu S, Asiedu C, Johnson J, Honko AN, Stanley D, Fabozzi G, Nichol ST, Ksiazek TG, Rollin PE, Wahl-Jensen V, Bailey M, Jahrling PB, Roederer M, Koup RA, Sullivan NJ. Demonstration of cross-protective vaccine immunity against an emerging pathogenic Ebolavirus species. PLoS Pathog 2010, 6:e1000904. 10.1371/journal.ppat.1000904, 2873919, 20502688.
58. Vanderzanden L, Bray M, Fuller D, Roberts T, Custer D, Spik K, Jahrling P, Huggins J, Schmaljohn A, Schmaljohn C. DNA vaccines expressing either the GP or NP genes of Ebola virus protect mice from lethal challenge. Virology 1998, 246:134-144. 10.1006/viro.1998.9176, 9657001.
59. Xu L, Sanchez A, Yang Z, Zaki SR, Nabel EG, Nichol ST, Nabel GJ. Immunization for Ebola virus infection. Nat Med 1998, 4:37-42. 10.1038/nm0198-037, 9427604.
60. Martin JE, Sullivan NJ, Enama ME, Gordon IJ, Roederer M, Koup RA, Bailer RT, Chakrabarti BK, Bailey MA, Gomez PL, Andrews CA, Moodie Z, Gu L, Stein JA, Nabel GJ, Graham BS. A DNA vaccine for Ebola virus is safe and immunogenic in a phase I clinical trial. Clin Vaccine Immunol 2006, 13:1267-1277. 10.1128/CVI.00162-06, 1656552, 16988008.
61. APHIS News: USDA issues license for West Nile DNA vaccine for horses. , http://www.aphis.usda.gov/lpa/news/2005/07/wnvdna_vs.html
62. Pratt WD, Wang D, Nichols DK, Luo M, Woraratanadharm J, Dye JM, Holman DH, Dong JY. Protection of nonhuman primates against two species of Ebola virus infection with a single complex adenovirus vector. Clin Vaccine Immunol 2010, 17:572-581. 10.1128/CVI.00467-09, 2849326, 20181765.
63. Ledgerwood JE, Costner P, Desai N, Holman L, Enama ME, Yamshchikov G, Mulangu S, Hu Z, Andrews CA, Sheets RA, Koup RA, Roederer M, Bailer R, Mascola JR, Pau MG, Sullivan NJ, Goudsmit J, Nabel GJ, Graham BS. A replication defective recombinant Ad5 vaccine expressing Ebola virus GP is safe and immunogenic in healthy adults. Vaccine 2010, 29:304-313. 10.1016/j.vaccine.2010.10.037, 21034824.
64. Vaccine development using recombinant DNA technology. Animal agriculture's future through biotechnology. , http://www.cast-science.org/websiteUploads/publicationPDFs/CAST%20Vaccine%20Development%20Issue%20Paper%20FINAL%20REV153.pdf
65. Jones SM, Feldmann H, Stroher U, Geisbert JB, Fernando L, Grolla A, Klenk HD, Sullivan NJ, Volchkov VE, Fritz EA, Daddario KM, Hensley LE, Jahrling PB, Geisbert TW. Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses. Nat Med 2005, 11:786-790. 10.1038/nm1258, 15937495.
66. Geisbert TW, Geisbert JB, Leung A, Daddario-DiCaprio KM, Hensley LE, Grolla A, Feldmann H. Single-injection vaccine protects nonhuman primates against infection with marburg virus and three species of ebola virus. J Virol 2009, 83:7296-7304. 10.1128/JVI.00561-09, 2704787, 19386702.
67. Feldmann H, Jones SM, Daddario-DiCaprio KM, Geisbert JB, Stroher U, Grolla A, Bray M, Fritz EA, Fernando L, Feldmann F, Hensley LE, Geisbert TW. Effective post-exposure treatment of Ebola infection. PLoS Pathog 2007, 3:e2. 10.1371/journal.ppat.0030002, 1779298, 17238284.
68. Geisbert TW, Daddario-DiCaprio KM, Williams KJ, Geisbert JB, Leung A, Feldmann F, Hensley LE, Feldmann H, Jones SM. Recombinant vesicular stomatitis virus vector mediates postexposure protection against Sudan Ebola hemorrhagic fever in nonhuman primates. J Virol 2008, 82:5664-5668. 10.1128/JVI.00456-08, 2395203, 18385248.
69. Tuffs A. Experimental vaccine may have saved Hamburg scientist from Ebola fever. BMJ 2009, 338:b1223. 10.1136/bmj.b1223, 19307268.
70. Bukreyev A, Rollin PE, Tate MK, Yang L, Zaki SR, Shieh WJ, Murphy BR, Collins PL, Sanchez A. Successful topical respiratory tract immunization of primates against Ebola virus. J Virol 2007, 81:6379-6388. 10.1128/JVI.00105-07, 1900097, 17428868.
71. Warfield KL, Swenson DL, Olinger GG, Kalina WV, Aman MJ, Bavari S. Ebola virus-like particle-based vaccine protects nonhuman primates against lethal Ebola virus challenge. J Infect Dis 2007, 196(Suppl 2):S430-S437. 10.1086/520583, 17940980.
72. Halfmann P, Ebihara H, Marzi A, Hatta Y, Watanabe S, Suresh M, Neumann G, Feldmann H, Kawaoka Y. Replication-deficient ebolavirus as a vaccine candidate. J Virol 2009, 83:3810-3815. 10.1128/JVI.00074-09, 2663241, 19211761.
73. Huggins JW. Prospects for treatment of viral hemorrhagic fevers with ribavirin, a broad-spectrum antiviral drug. Rev Infect Dis 1989, 11(Suppl 4):S750-S761.
74. Jahrling PB, Geisbert TW, Geisbert JB, Swearengen JR, Bray M, Jaax NK, Huggins JW, LeDuc JW, Peters CJ. Evaluation of immune globulin and recombinant interferon-alpha2b for treatment of experimental Ebola virus infections. J Infect Dis 1999, 179(Suppl 1):S224-S234. 10.1086/514310, 9988188.
75. Hensley LE, Stevens EL, Yan SB, Geisbert JB, Macias WL, Larsen T, Daddario-DiCaprio KM, Cassell GH, Jahrling PB, Geisbert TW. Recombinant human activated protein C for the postexposure treatment of Ebola hemorrhagic fever. J Infect Dis 2007, 196(Suppl 2):S390-S399. 10.1086/520598, 17940975.
76. Geisbert TW, Hensley LE, Jahrling PB, Larsen T, Geisbert JB, Paragas J, Young HA, Fredeking TM, Rote WE, Vlasuk GP. Treatment of Ebola virus infection with a recombinant inhibitor of factor VIIa/tissue factor: a study in rhesus monkeys. Lancet 2003, 362:1953-1958. 10.1016/S0140-6736(03)15012-X, 14683653.
77. Oswald WB, Geisbert TW, Davis KJ, Geisbert JB, Sullivan NJ, Jahrling PB, Parren PW, Burton DR. Neutralizing antibody fails to impact the course of Ebola virus infection in monkeys. PLoS Pathog 2007, 3:e9. 10.1371/journal.ppat.0030009, 1779296, 17238286.
78. Volchkov VE, Volchkova VA, Muhlberger E, Kolesnikova LV, Weik M, Dolnik O, Klenk HD. Recovery of infectious Ebola virus from complementary DNA: RNA editing of the GP gene and viral cytotoxicity. Science 2001, 291:1965-1969. 10.1126/science.1057269, 11239157.
79. Towner JS, Paragas J, Dover JE, Gupta M, Goldsmith CS, Huggins JW, Nichol ST. Generation of eGFP expressing recombinant Zaire ebolavirus for analysis of early pathogenesis events and high-throughput antiviral drug screening. Virology 2005, 332:20-27. 10.1016/j.virol.2004.10.048, 15661137.
80. Ebihara H, Theriault S, Neumann G, Alimonti JB, Geisbert JB, Hensley LE, Groseth A, Jones SM, Geisbert TW, Kawaoka Y, Feldmann H. In vitro and in vivo characterization of recombinant Ebola viruses expressing enhanced green fluorescent protein. J Infect Dis 2007, 196(Suppl 2):S313-S322. 10.1086/520590, 17940966.
81. Aman MJ, Kinch MS, Warfield K, Warren T, Yunus A, Enterlein S, Stavale E, Wang P, Chang S, Tang Q, Porter K, Goldblatt M, Bavari S. Development of a broad-spectrum antiviral with activity against Ebola virus. Antiviral Res 2009, 83:245-251. 10.1016/j.antiviral.2009.06.001, 19523489.
82. Kinch MS, Yunus AS, Lear C, Mao H, Chen H, Fesseha Z, Luo G, Nelson EA, Li L, Huang Z, Murray M, Ellis WY, Hensley L, Christopher-Hennings J, Olinger GG, Goldblatt M. FGI-104: a broad-spectrum small molecule inhibitor of viral infection. Am J Transl Res 2009, 1:87-98. 2776286, 19966942.
83. Warren TK, Warfield KL, Wells J, Enterlein S, Smith M, Ruthel G, Yunus AS, Kinch MS, Goldblatt M, Aman MJ, Bavari S. Antiviral activity of a small-molecule inhibitor of filovirus infection. Antimicrob Agents Chemother 2010, 54:2152-2159. 10.1128/AAC.01315-09, 2863630, 20211898.
84. Wolf MC, Freiberg AN, Zhang T, Akyol-Ataman Z, Grock A, Hong PW, Li J, Watson NF, Fang AQ, Aguilar HC, Porotto M, Honko AN, Damoiseaux R, Miller JP, Woodson SE, Chantasirivisal S, Fontanes V, Negrete OA, Krogstad P, Dasgupta A, Moscona A, Hensley LE, Whelan SP, Faull KF, Holbrook MR, Jung ME, Lee B. A broad-spectrum antiviral targeting entry of enveloped viruses. Proc Natl Acad Sci USA 2010, 107:3157-3162. 10.1073/pnas.0909587107, 2840368, 20133606.
85. Geisbert TW, Hensley LE, Kagan E, Yu EZ, Geisbert JB, Daddario-DiCaprio K, Fritz EA, Jahrling PB, McClintock K, Phelps JR, Lee AC, Judge A, Jeffs LB, MacLachlan I. Postexposure protection of guinea pigs against a lethal ebola virus challenge is conferred by RNA interference. J Infect Dis 2006, 193:1650-1657. 10.1086/504267, 16703508.
86. Geisbert TW, Lee AC, Robbins M, Geisbert JB, Honko AN, Sood V, Johnson JC, de Jong S, Tavakoli I, Judge A, Hensley LE, Maclachlan I. Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: a proof-of-concept study. Lancet 2010, 375:1896-1905. 10.1016/S0140-6736(10)60357-1, 20511019.
87. Warfield KL, Swenson DL, Olinger GG, Nichols DK, Pratt WD, Blouch R, Stein DA, Aman MJ, Iversen PL, Bavari S. Gene-specific countermeasures against Ebola virus based on antisense phosphorodiamidate morpholino oligomers. PLoS Pathog 2006, 2:e1. 10.1371/journal.ppat.0020001, 1326218, 16415982.
88. Warren TK, Warfield KL, Wells J, Swenson DL, Donner KS, Van Tongeren SA, Garza NL, Dong L, Mourich DV, Crumley S, Nichols DK, Iversen PL, Bavari S. Advanced antisense therapies for postexposure protection against lethal filovirus infections. Nat Med 2010, 16:991-994. 10.1038/nm.2202, 20729866.
89. Kash JC. Applications of high-throughput genomics to antiviral research: evasion of antiviral responses and activation of inflammation during fulminant RNA virus infection. Antiviral Res 2009, 83:10-20. 10.1016/j.antiviral.2009.04.004, 19375457.
90. Rappuoli R. Reverse vaccinology, a genome-based approach to vaccine development. Vaccine 2001, 19:2688-2691. 10.1016/S0264-410X(00)00554-5, 11257410.
91. Gomis-Roth FX, Dessen A, Timmins J, Bracher A, Kolesnikowa L, Becker S, Klenk HD, Weissenhorn W. The matrix protein VP40 from Ebola virus octamerizes into pore-like structures with specific RNA binding properties. Structure 2003, 11:423-433. 10.1016/S0969-2126(03)00050-9, 12679020.
92. Lee JE, Fusco ML, Hessell AJ, Oswald WB, Burton DR, Saphire EO. Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor. Nature 2008, 454:177-182. 10.1038/nature07082, 2700032, 18615077.
93. Lee JE, Kuehne A, Abelson DM, Fusco ML, Hart MK, Saphire EO. Complex of a protective antibody with its Ebola virus GP peptide epitope: unusual features of a V lambda(x) light chain. J Mol Biol 2008, 375:202-216. 10.1016/j.jmb.2007.10.017, 2173910, 18005986.
94. Leung DW, Shabman RS, Farahbakhsh M, Prins KC, Borek DM, Wang TJ, Muhlberger E, Basler CF, Amarasinghe GK. Structural and functional characterization of Reston Ebola virus VP35 interferon inhibitory domain. J Mol Biol 2010, 399:347-357. 10.1016/j.jmb.2010.04.022, 20399790.
95. MacGill T, Schrager L, Mathis M, Pelsor F, Shapiro A, Cress L, Leissa B, Roberts R. Development of drug medical countermeasures through the "animal rule". Chem-Biol Interact 2006, 161:197.
96. Roberts R, McCune SK. Animal studies in the development of medical countermeasures. Clin Pharmacol Ther 2008, 83:918-920. 10.1038/clpt.2008.23, 18323860.
97. Sullivan NJ, Martin JE, Graham BS, Nabel GJ. Correlates of protective immunity for Ebola vaccines: implications for regulatory approval by the animal rule. Nat Rev Microbiol 2009, 7:393-400. 10.1038/nrmicro2129, 19369954.