Publikationsserver der Universitätsbibliothek Marburg

Titel:Funktionelle Charakterisierung der cytoplasmatischen Domäne des Marburgvirus Oberflächenproteins GP
Autor:Mittler, Eva-Maria
Weitere Beteiligte: Lingelbach, Klaus (Prof.Dr.)
Veröffentlicht:2009
URI:https://archiv.ub.uni-marburg.de/diss/z2010/0487
URN: urn:nbn:de:hebis:04-z2010-04875
DOI: https://doi.org/10.17192/z2010.0487
DDC: Biowissenschaften, Biologie
Titel (trans.):Functional characterization of the cytoplasmic domain of the Marburg virus surface protein GP
Publikationsdatum:2010-09-22
Lizenz:https://rightsstatements.org/vocab/InC-NC/1.0/

Dokument

Schlagwörter:
Virus entry, Marburg-Virus-Krankheit, Viruseintritt, Marburg virus, Virus-like particle assay, Glycoprotein, Glykoprotein, Virus-like particle System

Zusammenfassung:
Das Marburgvirus (MARV) bildet zusammen mit dem Ebolavirus die Familie der Filoviridae, welche in menschlichen und nicht-menschlichen Primaten schwere hämorraghische Fieber verursachen können. Die Infektion von Zielzellen wird dabei durch das einzige Oberflächen-protein des MARV, das Glykoprotein GP vermittelt. Das Glykoprotein induziert die Bindung viraler Partikel an den zellulären Rezeptor, mit darauf folgender Endozytose, Fusion der viralen mit der endosomalen Membran, Freisetzung des Nukleocapsids in das Cytoplasma und darauf folgend Transkription und Replikation der viralen RNA. Bei dem MARV GP handelt es sich um ein klassisches Typ I Transmembranprotein bestehend aus einer großen Ektodomäne (220 kDa), einer Transmembran- und einer sehr kurzen cytoplasmatischen Domäne. Die Funktionen der Ekto- und Transmembrandomäne des MARV GP für den viralen Lebenszyklus wurden bereits weit reichend untersucht. Die Aufgabe der cytoplasmatischen Domäne des GP blieb bislang ungeklärt, möglicherweise weil die aus acht Aminosäuren aufgebaute Domäne keine klassischen Signalsequenzen enthält, die z.B. den intrazellulären Transport oder die Assemblierung und Ausschleusung viraler Partikel beeinflussen könnten. Im Laufe dieser Studie konnte gezeigt werden, dass die cytoplasmatische Domäne den intrazellulären Transport des MARV GP entlang des klassischen sekretorischen Transport-wegs an die Plasmamembran nicht unmittelbar beeinflusst. Dies war erkennbar an den posttranslationalen Modifikationen wie N-Glykosylierung oder Oligomerisierung des GP, welche auch in Abwesenheit der cytoplasmatischen Domäne (GPΔCD) nicht signifikant verändert waren. Der Einfluss der cytoplasmatischen Domäne des GP auf den Zusammen-bau, Freisetzung und Infektiosität von MARV wurde mittels MARV-spezifischer infektiöser Virus-ähnlicher Partikel (iVLP) untersucht, die als Modellsystem für eine natürliche MARV Infektion gelten. Mittels quantitativer Immunelektronenmikroskopie wurde gezeigt, dass die cytoplasmatische Domäne des GP den Einbau des Proteins in iVLPs, als auch deren filamentöse Morphologie nicht beeinflusste, jedoch die erzeugten iVLPs eine deutlich reduzierte Infektiosität aufzeigten. Die zeitgleich auftretende verminderte O-Glykosylierung des GPΔCD wurde als ein Indiz für eine Konformationsänderung in der Ektodomäne angesehen, induziert durch die Abwesenheit der cytoplasmatischen Domäne. Mit Hilfe eines neu etablierten Aufnahmeassays konnte nachgewiesen werden, dass GPΔCD neben einer verringerten Infektiosität von iVLPs, auch deren verminderte Aufnahme in Ziel-zellen induzierte. Wir nehmen an, dass die Abwesenheit der cytoplasmatischen Domäne des Glykoproteins eine Konformationsänderung der Ektodomäne induziert (so genanntes „inside-out signaling“), was in einer verringerten Fusionsaktivität des GP und damit reduzierten Infektiosität resultiert.

Bibliographie / References

  1. Laemmli, U. K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227(5259), 680-5.
  2. Voß, D. (2007). Glykosylierung und intrazellulärer Transport des SARS-Coronavirus Membranproteins. Dissertation.
  3. Wenigenrath, J. (2008). Etablierung eines infektiösen Minigenomsystems für Marburg Virus basierend auf Virus-ähnlichen Partikeln. Dissertation.
  4. Ignowski, J. M., and Schaffer, D. V. (2004). Kinetic analysis and modeling of firefly luciferase as a quantitative reporter gene in live mammalian cells. Biotechnol Bioeng 86(7), 827-34.
  5. Sanderson, C. M., McQueen, N. L., and Nayak, D. P. (1993). Sendai virus assembly: M protein binds to viral glycoproteins in transit through the secretory pathway. J Virol 67(2), 651-63.
  6. Wild, T. F., Malvoisin, E., and Buckland, R. (1991). Measles virus: both the haemagglutinin and fusion glycoproteins are required for fusion. J Gen Virol 72 ( Pt 2), 439-42.
  7. Licata, J. M., Johnson, R. F., Han, Z., and Harty, R. N. (2004). Contribution of ebola virus glycoprotein, nucleoprotein, and VP24 to budding of VP40 virus-like particles. J Virol 78(14), 7344-51.
  8. Mellquist-Riemenschneider, J. L., Garrison, A. R., Geisbert, J. B., Saikh, K. U., Heidebrink, K. D., Jahrling, P. B., Ulrich, R. G., and Schmaljohn, C. S. (2003). Comparison of the protective efficacy of DNA and baculovirus-derived protein vaccines for EBOLA virus in guinea pigs. Virus Res 92(2), 187-93.
  9. Volchkov, V. E., Volchkova, V. A., Stroher, U., Becker, S., Dolnik, O., Cieplik, M., Garten, W., Klenk, H. D., and Feldmann, H. (2000b). Proteolytic processing of Marburg virus glycoprotein. Virology 268(1), 1-6.
  10. Ryabchikova, E. I., Kolesnikova, L. V., and Netesov, S. V. (1999). Animal pathology of filoviral infections. Curr Top Microbiol Immunol 235, 145-73.
  11. Garcia-Sastre, A., and Palese, P. (1995). The cytoplasmic tail of the neuraminidase protein of influenza A virus does not play an important role in the packaging of this protein into viral envelopes. Virus Res 37(1), 37-47.
  12. Geisbert, T. W., and Jahrling, P. B. (1995). Differentiation of filoviruses by electron microscopy. Virus Res 39(2-3), 129-50.
  13. Modrof, J., Muhlberger, E., Klenk, H. D., and Becker, S. (2002). Phosphorylation of VP30 impairs ebola virus transcription. J Biol Chem 277(36), 33099-104.
  14. Mupapa, K., Massamba, M., Kibadi, K., Kuvula, K., Bwaka, A., Kipasa, M., Colebunders, R., and Muyembe-Tamfum, J. J. (1999). Treatment of Ebola hemorrhagic fever with blood transfusions from convalescent patients. International Scientific and Technical Committee. J Infect Dis 179 Suppl 1, S18-23.
  15. Miranda, M. E., Ksiazek, T. G., Retuya, T. J., Khan, A. S., Sanchez, A., Fulhorst, C. F., Rollin, P. E., Calaor, A. B., Manalo, D. L., Roces, M. C., Dayrit, M. M., and Peters, C. J. (1999). Epidemiology of Ebola (subtype Reston) virus in the Philippines, 1996. J Infect Dis 179 Suppl 1, S115-9.
  16. Pourrut, X., Delicat, A., Rollin, P. E., Ksiazek, T. G., Gonzalez, J. P., and Leroy, E. M. (2007). Spatial and temporal patterns of Zaire ebolavirus antibody prevalence in the possible reservoir bat species. J Infect Dis 196 Suppl 2, S176-83.
  17. Ebola virus-like particle-based vaccine protects nonhuman primates against lethal Ebola virus challenge. J Infect Dis 196 Suppl 2, S430-7.
  18. Kolesnikova, L., Ryabchikova, E., Shestopalov, A., and Becker, S. (2007b). Basolateral budding of Marburg virus: VP40 retargets viral glycoprotein GP to the basolateral surface. J Infect Dis 196 Suppl 2, S232-6.
  19. Jones, S. M., Stroher, U., Fernando, L., Qiu, X., Alimonti, J., Melito, P., Bray, M., Klenk, H. D., and Feldmann, H. (2007). Assessment of a vesicular stomatitis virus-based vaccine by use of the mouse model of Ebola virus hemorrhagic fever. J Infect Dis 196 Suppl 2, S404-12.
  20. Noda, T., Halfmann, P., Sagara, H., and Kawaoka, Y. (2007). Regions in Ebola virus VP24 that are important for nucleocapsid formation. J Infect Dis 196 Suppl 2, S247-50.
  21. Sanchez, A. (2007). Analysis of filovirus entry into vero e6 cells, using inhibitors of endocytosis, endosomal acidification, structural integrity, and cathepsin (B and L) activity. J Infect Dis 196 Suppl 2, S251-8.
  22. Geisbert, T. W., Daddario-DiCaprio, K. M., Geisbert, J. B., Young, H. A., Formenty, P., Fritz, E. A., Larsen, T., and Hensley, L. E. (2007). Marburg virus Angola infection of rhesus macaques: pathogenesis and treatment with recombinant nematode anticoagulant protein c2. J Infect Dis 196 Suppl 2, S372-81.
  23. Sureau, P. H. (1989). Firsthand clinical observations of hemorrhagic manifestations in Ebola hemorrhagic fever in Zaire. Rev Infect Dis 11 Suppl 4, S790-3.
  24. Scianimanico, S., Schoehn, G., Timmins, J., Ruigrok, R. H., Klenk, H. D., and Weissenhorn, W. (2000). Membrane association induces a conformational change in the Ebola virus matrix protein. Embo J 19(24), 6732-41.
  25. Feng, Z., Cerveny, M., Yan, Z., and He, B. (2007). The VP35 protein of Ebola virus inhibits the antiviral effect mediated by double-stranded RNA-dependent protein kinase PKR. J Virol 81(1), 182-92.
  26. Martinez, M. J., Biedenkopf, N., Volchkova, V., Hartlieb, B., Alazard-Dany, N., Reynard, O., Becker, S., and Volchkov, V. (2008). Role of Ebola virus VP30 in transcription reinitiation. J Virol 82(24), 12569-73.
  27. Johnson, R. F., McCarthy, S. E., Godlewski, P. J., and Harty, R. N. (2006b). Ebola virus VP35-VP40 interaction is sufficient for packaging 3E-5E minigenome RNA into virus-like particles. J Virol 80(11), 5135-44.
  28. Prins, K. C., Cardenas, W. B., and Basler, C. F. (2009). Ebola virus protein VP35 impairs the function of interferon regulatory factor-activating kinases IKKepsilon and TBK-1. J Virol 83(7), 3069-77.
  29. Cardenas, W. B., Loo, Y. M., Gale, M., Jr., Hartman, A. L., Kimberlin, C. R., Martinez- Sobrido, L., Saphire, E. O., and Basler, C. F. (2006). Ebola virus VP35 protein binds double-stranded RNA and inhibits alpha/beta interferon production induced by RIG-I signaling. J Virol 80(11), 5168-78.
  30. Modrof, J., Becker, S., and Muhlberger, E. (2003). Ebola virus transcription activator VP30 is a zinc-binding protein. J Virol 77(5), 3334-8.
  31. Mahanty, S., Hutchinson, K., Agarwal, S., McRae, M., Rollin, P. E., and Pulendran, B. (2003). Cutting edge: impairment of dendritic cells and adaptive immunity by Ebola and Lassa viruses. J Immunol 170(6), 2797-801.
  32. Fowler, T., Bamberg, S., Moller, P., Klenk, H. D., Meyer, T. F., Becker, S., and Rudel, T. (2005). Inhibition of Marburg virus protein expression and viral release by RNA interference. J Gen Virol 86(Pt 4), 1181-8.
  33. Le Guenno, F. P., Boesch C. (1999). Ebola virus outbreaks in the Ivory Coast and Liberia, 1994-1995. Curr Top Microbiol Immunol. 235, 77-84.
  34. Richardson, J. S., Yao, M. K., Tran, K. N., Croyle, M. A., Strong, J. E., Feldmann, H., and Kobinger, G. P. (2009). Enhanced protection against Ebola virus mediated by an improved adenovirus-based vaccine. PLoS ONE 4(4), e5308.
  35. Geisbert, T. W., Young, H. A., Jahrling, P. B., Davis, K. J., Kagan, E., and Hensley, L. E. (2003b). 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), 1618-29.
  36. Noda, T., Sagara, H., Suzuki, E., Takada, A., Kida, H., and Kawaoka, Y. (2002). Ebola virus VP40 drives the formation of virus-like filamentous particles along with GP. J Virol 76(10), 4855-65.
  37. Lin, G., Simmons, G., Pohlmann, S., Baribaud, F., Ni, H., Leslie, G. J., Haggarty, B. S., Bates, P., Weissman, D., Hoxie, J. A., and Doms, R. W. (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), 1337-46.
  38. Fischer, C., Schroth-Diez, B., Herrmann, A., Garten, W., and Klenk, H. D. (1998). Acylation of the influenza hemagglutinin modulates fusion activity. Virology 248(2), 284-94.
  39. Funke, C., Becker, S., Dartsch, H., Klenk, H. D., and Muhlberger, E. (1995). Acylation of the Marburg virus glycoprotein. Virology 208(1), 289-97.
  40. Martini, K. H., Schmidt HA, Mayer G, Baltzer G. (1968). A hitherto unknown infectious disease contracted from monkeys. "Marburg-virus" disease. Ger Med Mon 13(10), 457- 70.
  41. Schornberg, K. L., Shoemaker, C. J., Dube, D., Abshire, M. Y., Delos, S. E., Bouton, A. H., and White, J. M. (2009). Alpha5beta1-integrin controls ebolavirus entry by regulating endosomal cathepsins. Proc Natl Acad Sci U S A 106(19), 8003-8.
  42. Sanchez, A., Lukwiya, M., Bausch, D., Mahanty, S., Sanchez, A. J., Wagoner, K. D., and Rollin, P. E. (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), 10370-7.
  43. Pokhodiaev, V. A., Gonchar, N. I., and Pshenichnov, V. A. (1991). [An experimental study of the contact transmission of the Marburg virus]. Vopr Virusol 36(6), 506-8.
  44. Wei, X., Decker, J. M., Wang, S., Hui, H., Kappes, J. C., Wu, X., Salazar-Gonzalez, J. F., Salazar, M. G., Kilby, J. M., Saag, M. S., Komarova, N. L., Nowak, M. A., Hahn, B. H., Kwong, P. D., and Shaw, G. M. (2003). Antibody neutralization and escape by HIV-1. Nature 422(6929), 307-12.
  45. Harty, R. N., Brown, M. E., Wang, G., Huibregtse, J., and Hayes, F. P. (2000). A PPxY motif within the VP40 protein of Ebola virus interacts physically and functionally with a ubiquitin ligase: implications for filovirus budding. Proc Natl Acad Sci U S A 97(25), 13871-6.
  46. Nayak, D. P., Hui, E. K., and Barman, S. (2004). Assembly and budding of influenza virus. Virus Res 106(2), 147-65.
  47. Association of ebola virus matrix protein VP40 with microtubules. J Virol 79(8), 4709-19.
  48. Empig, C. J., and Goldsmith, M. A. (2002). Association of the caveola vesicular system with cellular entry by filoviruses. J Virol 76(10), 5266-70.
  49. Kolesnikova, L., Bohil, A. B., Cheney, R. E., and Becker, S. (2007a). Budding of Marburgvirus is associated with filopodia. Cell Microbiol 9(4), 939-51.
  50. Mebatsion, T., Konig, M., and Conzelmann, K. K. (1996). Budding of rabies virus particles in the absence of the spike glycoprotein. Cell 84(6), 941-51.
  51. WHO (2008). Case of Marburg Haemorrhagic Fever imported into the Netherlands from Uganda.
  52. Feldmann, H., Nichol, S. T., Klenk, H. D., Peters, C. J., and Sanchez, A. (1994). Characterization of filoviruses based on differences in structure and antigenicity of the virion glycoprotein. Virology 199(2), 469-73.
  53. Volchkov, V. E., Volchkova, V. A., Chepurnov, A. A., Blinov, V. M., Dolnik, O., Netesov, S. V., and Feldmann, H. (1999). Characterization of the L gene and 5' trailer region of Ebola virus. J Gen Virol 80 ( Pt 2), 355-62.
  54. Zhang, J., and Lamb, R. A. (1996). Characterization of the membrane association of the influenza virus matrix protein in living cells. Virology 225(2), 255-66. ANHANG 142
  55. Feldmann, H., and Kiley, M. P. (1999). Classification, structure, and replication of filoviruses. Curr Top Microbiol Immunol 235, 1-21.
  56. Riemenschneider, J., Garrison, A., Geisbert, J., Jahrling, P., Hevey, M., Negley, D., Schmaljohn, A., Lee, J., Hart, M. K., Vanderzanden, L., Custer, D., Bray, M., Ruff, A., Ivins, B., Bassett, A., Rossi, C., and Schmaljohn, C. (2003). Comparison of individual and combination DNA vaccines for B. anthracis, Ebola virus, Marburg virus and Venezuelan equine encephalitis virus. Vaccine 21(25-26), 4071-80.
  57. Muhlberger, E., Weik, M., Volchkov, V. E., Klenk, H. D., and 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), 2333-42.
  58. Wang, D., Hevey, M., Juompan, L. Y., Trubey, C. M., Raja, N. U., Deitz, S. B., Woraratanadharm, J., Luo, M., Yu, H., Swain, B. M., Moore, K. M., and Dong, J. Y. (2006a). Complex adenovirus-vectored vaccine protects guinea pigs from three strains of Marburg virus challenges. Virology 353(2), 324-32.
  59. Crystallization and preliminary X-ray analysis of the matrix protein from Ebola virus. Acta Crystallogr D Biol Crystallogr 56(Pt 6), 758-60.
  60. Hartlieb, B., Muziol, T., Weissenhorn, W., and Becker, S. (2007). Crystal structure of the C- terminal domain of Ebola virus VP30 reveals a role in transcription and nucleocapsid association. Proc Natl Acad Sci U S A 104(2), 624-9.
  61. Weissenhorn, W., Carfi, A., Lee, K. H., Skehel, J. J., and Wiley, D. C. (1998b). Crystal structure of the Ebola virus membrane fusion subunit, GP2, from the envelope glycoprotein ectodomain. Mol Cell 2(5), 605-16.
  62. Dessen, A., Volchkov, V., Dolnik, O., Klenk, H. D., and Weissenhorn, W. (2000b). Crystal structure of the matrix protein VP40 from Ebola virus. Embo J 19(16), 4228-36.
  63. Levi, M. (2004). Current understanding of disseminated intravascular coagulation. Br J Haematol 124(5), 567-76.
  64. Simmons, G., Reeves, J. D., Grogan, C. C., Vandenberghe, L. H., Baribaud, F., Whitbeck, J. C., Burke, E., Buchmeier, M. J., Soilleux, E. J., Riley, J. L., Doms, R. W., Bates, P., and Pohlmann, S. (2003a). DC-SIGN and DC-SIGNR bind ebola glycoproteins and enhance infection of macrophages and endothelial cells. Virology 305(1), 115-23.
  65. Marzi, A., Gramberg, T., Simmons, G., Moller, P., Rennekamp, A. J., Krumbiegel, M., Geier, M., Eisemann, J., Turza, N., Saunier, B., Steinkasserer, A., Becker, S., Bates, P., Hofmann, H., and Pohlmann, S. (2004). DC-SIGN and DC-SIGNR interact with the glycoprotein of Marburg virus and the S protein of severe acute respiratory syndrome coronavirus. J Virol 78(21), 12090-5.
  66. Elliott, L. H., Kiley, M. P., and McCormick, J. B. (1985). Descriptive analysis of Ebola virus proteins. Virology 147(1), 169-76.
  67. Wang, D., Raja, N. U., Trubey, C. M., Juompan, L. Y., Luo, M., Woraratanadharm, J., Deitz, S. B., Yu, H., Swain, B. M., Moore, K. M., Pratt, W. D., Hart, M. K., and Dong, J. Y. (2006b). Development of a cAdVax-based bivalent ebola virus vaccine that induces immune responses against both the Sudan and Zaire species of Ebola virus. J Virol 80(6), 2738-46.
  68. Sullivan, N. J., Sanchez, A., Rollin, P. E., Yang, Z. Y., and Nabel, G. J. (2000). Development of a preventive vaccine for Ebola virus infection in primates. Nature 408(6812), 605-9.
  69. Moore, J. P., McKeating, J. A., Weiss, R. A., and Sattentau, Q. J. (1990). Dissociation of gp120 from HIV-1 virions induced by soluble CD4. Science 250(4984), 1139-42.
  70. WHO (1978). Ebola haemorrhagic fever in Sudan, 1976. Report of a WHO/International Study Team. Bull World Health Organ 56(2), 247-70.
  71. WHO (2004a). Ebola haemorrhagic fever in the Republic of the Congo -update 6.
  72. WHO (1996). Ebola-Reston virus infection among quarantined nonhuman primates--Texas, 1996. MMWR Morb Mortal Wkly Rep 45(15), 314-6.
  73. CDC, C. f. D. C. a. P. (1989). Ebola virus infection in imported primates--Virginia, 1989. MMWR Morb Mortal Wkly Rep. 38(48), 831-2; 837-8.
  74. Timmins, J., Schoehn, G., Ricard-Blum, S., Scianimanico, S., Vernet, T., Ruigrok, R. W., and Weissenhorn, W. (2003). Ebola virus matrix protein VP40 interaction with human cellular factors Tsg101 and Nedd4. J Mol Biol 326(2), 493-502.
  75. Formenty, P., Boesch, C., Wyers, M., Steiner, C., Donati, F., Dind, F., Walker, F., and Le Guenno, B. (1999). Ebola virus outbreak among wild chimpanzees living in a rain forest of Cote d'Ivoire. J Infect Dis 179 Suppl 1, S120-6.
  76. Harcourt, B. H., Sanchez, A., and Offermann, M. K. (1999). Ebola virus selectively inhibits responses to interferons, but not to interleukin-1beta, in endothelial cells. J Virol 73(4), 3491-6.
  77. Reid, S. P., Leung, L. W., Hartman, A. L., Martinez, O., Shaw, M. L., Carbonnelle, C., Volchkov, V. E., Nichol, S. T., and Basler, C. F. (2006). Ebola virus VP24 binds karyopherin alpha1 and blocks STAT1 nuclear accumulation. J Virol 80(11), 5156-67.
  78. Weik, M., Modrof, J., Klenk, H. D., Becker, S., and Muhlberger, E. (2002). Ebola virus VP30- mediated transcription is regulated by RNA secondary structure formation. J Virol 76(17), 8532-9.
  79. Feldmann, S. W., Klenk HD. (1996b). Emerging and reemerging of filoviruses. Arch Virol Suppl. 11, 77-100.
  80. Normile, D. (2009). Emerging infectious diseases. Scientists puzzle over Ebola-Reston virus in pigs. Science 323(5913), 451.
  81. WHO (2009a). End of Ebola outbreak in the Democratic Republic of the Congo.
  82. Geisbert, T. W., Pushko, P., Anderson, K., Smith, J., Davis, K. J., and Jahrling, P. B. (2002). Evaluation in nonhuman primates of vaccines against Ebola virus. Emerg Infect Dis 8(5), 503-7.
  83. Jahrling, P. B., Geisbert, T. W., Jaax, N. K., Hanes, M. A., Ksiazek, T. G., and Peters, C. J. (1996). Experimental infection of cynomolgus macaques with Ebola-Reston filoviruses from the 1989-1990 U.S. epizootic. Arch Virol Suppl 11, 115-34.
  84. Odorizzi, G., Babst, M., and Emr, S. D. (1998). Fab1p PtdIns(3)P 5-kinase function essential for protein sorting in the multivesicular body. Cell 95(6), 847-58.
  85. Filoviridae: a taxonomic home for Marburg and Ebola viruses? Intervirology 18(1-2), 24- 32.
  86. Fisher-Hoch, S. P., Perez-Oronoz, G. I., Jackson, E. L., Hermann, L. M., and Brown, B. G. (1992). Filovirus clearance in non-human primates. Lancet 340(8817), 451-3.
  87. Dolnik, O., Kolesnikova, L., and Becker, S. (2008). Filoviruses: Interactions with the host cell. Cell Mol Life Sci 65(5), 756-76.
  88. Chan, S. Y., Empig, C. J., Welte, F. J., Speck, R. F., Schmaljohn, A., Kreisberg, J. F., and Goldsmith, M. A. (2001). Folate receptor-alpha is a cofactor for cellular entry by Marburg and Ebola viruses. Cell 106(1), 117-26.
  89. CDC, C. f. D. C. a. P. (1995). From the Centers for Disease Control and Prevention. Update: outbreak of Ebola viral hemorrhagic fever--Zaire, 1995. JAMA 274(5), 373-4.
  90. Leroy, E. M., Kumulungui, B., Pourrut, X., Rouquet, P., Hassanin, A., Yaba, P., Delicat, A., Paweska, J. T., Gonzalez, J. P., and Swanepoel, R. (2005). Fruit bats as reservoirs of Ebola virus. Nature 438(7068), 575-6.
  91. Lee, J. K., Prussia, A., Paal, T., White, L. K., Snyder, J. P., and Plemper, R. K. (2008b). Functional interaction between paramyxovirus fusion and attachment proteins. J Biol Chem 283(24), 16561-72.
  92. Hoenen (2006). Function of the viral matrix proteins VP40 and VP24 for the life cycle of Ebolavirus. Dissertation.
  93. Swenson, D. L., Warfield, K. L., Kuehl, K., Larsen, T., Hevey, M. C., Schmaljohn, A., Bavari, S., and Aman, M. J. (2004). Generation of Marburg virus-like particles by co-expression of glycoprotein and matrix protein. FEMS Immunol Med Microbiol 40(1), 27-31.
  94. Feldmann, H., Will, C., Schikore, M., Slenczka, W., and Klenk, H. D. (1991). Glycosylation and oligomerization of the spike protein of Marburg virus. Virology 182(1), 353-6.
  95. Volchkov, V. E., Becker, S., Volchkova, V. A., Ternovoj, V. A., Kotov, A. N., Netesov, S. V., and Klenk, H. D. (1995). GP mRNA of Ebola virus is edited by the Ebola virus polymerase and by T7 and vaccinia virus polymerases. Virology 214(2), 421-30.
  96. Martin-Serrano, J., Zang, T., and Bieniasz, P. D. (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), 1313-9.
  97. Moller, P., Pariente, N., Klenk, H. D., and Becker, S. (2005). Homo-oligomerization of Marburgvirus VP35 is essential for its function in replication and transcription. J Virol 79(23), 14876-86.
  98. Leroy, E. M., Epelboin, A., Mondonge, V., Pourrut, X., Gonzalez, J. P., Muyembe-Tamfum, J. J., and Formenty, P. (2009). Human Ebola Outbreak Resulting from Direct Exposure to Fruit Bats in Luebo, Democratic Republic of Congo, 2007. Vector Borne Zoonotic Dis.
  99. Mittler, E. (2005). Identifizierung der Transmembrandomäne des Marburgvirus Oberflächenproteins als endosomales Sortierungssignal. Diplomarbeit.
  100. Hoenen, T., Groseth, A., Kolesnikova, L., Theriault, S., Ebihara, H., Hartlieb, B., Bamberg, S., Feldmann, H., Stroher, U., and Becker, S. (2006). Infection of naive target cells with virus-like particles: implications for the function of ebola virus VP24. J Virol 80(14), 7260- 4.
  101. Enami, M., and Enami, K. (1996). Influenza virus hemagglutinin and neuraminidase glycoproteins stimulate the membrane association of the matrix protein. J Virol 70(10), 6653-7.
  102. Johnson, K. M., Lange, J. V., Webb, P. A., and Murphy, F. A. (1977). Isolation and partial characterisation of a new virus causing acute haemorrhagic fever in Zaire. Lancet 1(8011), 569-71.
  103. Pattyn, S., van der Groen, G., Courteille, G., Jacob, W., and Piot, P. (1977). Isolation of Marburg-like virus from a case of haemorrhagic fever in Zaire. Lancet 1(8011), 573-4.
  104. Promotion am Fachbereich für Medizin, Institut für Virologie, Philipps-Universität, Marburg/Lahn in Kooperation mit dem Zentrum für biologische Sicherheit (ZBS), Robert-Koch Institut, Berlin Arbeitsgruppe: Prof. Dr. Stephan Becker Thema: " Funktionelle Charakterisierung der cytoplasmatischen Domäne des Marburgvirus Oberflächenproteins GP " Nov. 2004 -Aug. 2005
  105. Johnson, E., Jaax, N., White, J., and Jahrling, P. (1995). Lethal experimental infections of rhesus monkeys by aerosolized Ebola virus. Int J Exp Pathol 76(4), 227-36.
  106. LSECtin interacts with filovirus glycoproteins and the spike protein of SARS coronavirus. Virology 340(2), 224-36.
  107. Schnittler, H. J., and Feldmann, H. (1998). Marburg and Ebola hemorrhagic fevers: does the primary course of infection depend on the accessibility of organ-specific macrophages? Clin Infect Dis 27(2), 404-6.
  108. Simpson, D. I. (1977). Marburg fever. Nurs Mirror 144(21), 13-5.
  109. Ndayimirije, N., and Kindhauser, M. K. (2005). Marburg hemorrhagic fever in Angola-- fighting fear and a lethal pathogen. N Engl J Med 352(21), 2155-7.
  110. Feldmann, H., Muhlberger, E., Randolf, A., Will, C., Kiley, M. P., Sanchez, A., and Klenk, H. D. (1992). Marburg virus, a filovirus: messenger RNAs, gene order, and regulatory elements of the replication cycle. Virus Res 24(1), 1-19.
  111. Will, C., Muhlberger, E., Linder, D., Slenczka, W., Klenk, H. D., and Feldmann, H. (1993). Marburg virus gene 4 encodes the virion membrane protein, a type I transmembrane glycoprotein. J Virol 67(3), 1203-10.
  112. Towner, J. S., Pourrut, X., Albarino, C. G., Nkogue, C. N., Bird, B. H., Grard, G., Ksiazek, T. G., Gonzalez, J. P., Nichol, S. T., and Leroy, E. M. (2007). Marburg virus infection detected in a common African bat. PLoS ONE 2(1), e764.
  113. Warfield, K. L., Swenson, D. L., Negley, D. L., Schmaljohn, A. L., Aman, M. J., and Bavari, S. (2004). Marburg virus-like particles protect guinea pigs from lethal Marburg virus infection. Vaccine 22(25-26), 3495-502.
  114. Hevey, M., Negley, D., Pushko, P., Smith, J., and Schmaljohn, A. (1998). Marburg virus vaccines based upon alphavirus replicons protect guinea pigs and nonhuman primates. Virology 251(1), 28-37.
  115. Hevey, M., Negley, D., VanderZanden, L., Tammariello, R. F., Geisbert, J., Schmaljohn, C., Smith, J. F., Jahrling, P. B., and Schmaljohn, A. L. (2001). Marburg virus vaccines: comparing classical and new approaches. Vaccine 20(3-4), 586-93.
  116. Villinger, F., Rollin, P. E., Brar, S. S., Chikkala, N. F., Winter, J., Sundstrom, J. B., Zaki, S. R., Swanepoel, R., Ansari, A. A., and Peters, C. J. (1999). 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 179 Suppl 1, S188-91.
  117. Mebatsion, T., Weiland, F., and Conzelmann, K. K. (1999). Matrix protein of rabies virus is responsible for the assembly and budding of bullet-shaped particles and interacts with the transmembrane spike glycoprotein G. J Virol 73(1), 242-50.
  118. Feldmann, H., Klenk, H. D., and Sanchez, A. (1993). Molecular biology and evolution of filoviruses. Arch Virol Suppl 7, 81-100.
  119. Volchkov, V. E., Chepurnov, A. A., Volchkova, V. A., Ternovoj, V. A., and Klenk, H. D. (2000a). Molecular characterization of guinea pig-adapted variants of Ebola virus. Virology 277(1), 147-55.
  120. Suzuki, N., Yamamoto, K., Toyoshima, S., Osawa, T., and Irimura, T. (1996). Molecular cloning and expression of cDNA encoding human macrophage C-type lectin. Its unique carbohydrate binding specificity for Tn antigen. J Immunol 156(1), 128-35.
  121. Mavrakis, M., Kolesnikova, L., Schoehn, G., Becker, S., and Ruigrok, R. W. (2002). Morphology of Marburg virus NP-RNA. Virology 296(2), 300-7.
  122. Qiu, X., Fernando, L., Alimonti, J. B., Melito, P. L., Feldmann, F., Dick, D., Stroher, U., Feldmann, H., and Jones, S. M. (2009). Mucosal immunization of cynomolgus macaques with the VSVDeltaG/ZEBOVGP vaccine stimulates strong ebola GP-specific immune responses. PLoS ONE 4(5), e5547.
  123. Multiple Ebola virus transmission events and rapid decline of central African wildlife. Science 303(5656), 387-90.
  124. Noda, T., Aoyama, K., Sagara, H., Kida, H., and Kawaoka, Y. (2005). Nucleocapsid-like structures of Ebola virus reconstructed using electron tomography. J Vet Med Sci 67(3), 325-8.
  125. Helenius, A., Kartenbeck, J., Simons, K., and Fries, E. (1980). On the entry of Semliki forest virus into BHK-21 cells. J Cell Biol 84(2), 404-20.
  126. Siegert, R., Shu, H.L., Slenczka, W., Peters, D., and Muller, G. (1967). On the etiology of an unknown human infection originating from monkeys. Dtsch Med Wochenschr 92(51), 2341-3.
  127. WHO (2009b). Outbreak news. Ebola Reston in pigs and humans, Philippines. Wkly Epidemiol Rec. 84(7), 49-50.
  128. CDC, C. f. D. C. a. P. (1996). Outbreak of Ebola haemorrhagic fever in Gabon. Commun Dis Rep CDR Wkly. 6(9), 75,78.
  129. WHO (2007). Outbreak of Marburg haemorrhagic fever: Uganda, June-August 2007. Wkly Epidemiol Rec. 82(43), 381-4.
  130. CDC, C. f. D. C. a. P. (2005). Outbreak of Marburg virus hemorrhagic fever--Angola, October 1, 2004-March 29, 2005. MMWR Morb Mortal Wkly Rep. 54(12), 308-9.
  131. Licata, J. M., Simpson-Holley, M., Wright, N. T., Han, Z., Paragas, J., and Harty, R. N. (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), 1812-9.
  132. Heminway, B. R., Yu, Y., and Galinski, M. S. (1994). Paramyxovirus mediated cell fusion requires co-expression of both the fusion and hemagglutinin-neuraminidase glycoproteins. Virus Res 31(1), 1-16.
  133. Geisbert, T. W., Young, H. A., Jahrling, P. B., Davis, K. J., Larsen, T., Kagan, E., and Hensley, L. E. (2003c). 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), 2371-82.
  134. Kiley, M. P., Cox, N. J., Elliott, L. H., Sanchez, A., DeFries, R., Buchmeier, M. J., Richman, D. D., and McCormick, J. B. (1988). Physicochemical properties of Marburg virus: evidence for three distinct virus strains and their relationship to Ebola virus. J Gen Virol 69 ( Pt 8), 1957-67.
  135. Posttranslationale Modifikationen des SARS-Coronavirus Membranproteins. Diplomarbeit.
  136. Procoagulant soluble tissue factor is released from endothelial cells in response to inflammatory cytokines. Circ Res 96(12), 1233-9.
  137. Katzmann, D. J., Odorizzi, G., and Emr, S. D. (2002). Receptor downregulation and multivesicular-body sorting. Nat Rev Mol Cell Biol 3(12), 893-905.
  138. Volchkov, V. E., Volchkova, V. A., Muhlberger, E., Kolesnikova, L. V., Weik, M., Dolnik, O., and Klenk, H. D. (2001). Recovery of infectious Ebola virus from complementary DNA: RNA editing of the GP gene and viral cytotoxicity. Science 291(5510), 1965-9.
  139. Strieter, R. M., Kunkel, S. L., and Bone, R. C. (1993). Role of tumor necrosis factor-alpha in disease states and inflammation. Crit Care Med 21(10 Suppl), S447-63.
  140. Sanchez, A., Kiley, M. P., Holloway, B. P., and Auperin, D. D. (1993). Sequence analysis of the Ebola virus genome: organization, genetic elements, and comparison with the genome of Marburg virus. Virus Res 29(3), 215-40.
  141. Sanchez, A., Kiley, M. P., Klenk, H. D., and Feldmann, H. (1992). Sequence analysis of the Marburg virus nucleoprotein gene: comparison to Ebola virus and other non-segmented negative-strand RNA viruses. J Gen Virol 73 ( Pt 2), 347-57.
  142. Poch, O., Blumberg, B. M., Bougueleret, L., and Tordo, N. (1990). Sequence comparison of five polymerases (L proteins) of unsegmented negative-strand RNA viruses: theoretical assignment of functional domains. J Gen Virol 71 ( Pt 5), 1153-62.
  143. Slenzcka, W., Rietschel, M., Hoffmann, C. and Sixl W. (1984). Seroepidemiologische Untersuchung über Vorkommen von Antikörpern gegen Marburg-und Ebola Virus in Afrika. Mitt. Oesterr. Ges. Tropenmed. Parasit 6, 53-60.
  144. Sorting of Marburg virus surface protein and virus release take place at opposite surfaces of infected polarized epithelial cells. J Virol 75(3), 1274-83.
  145. Feinberg, H., Mitchell, D. A., Drickamer, K., and Weis, W. I. (2001). Structural basis for selective recognition of oligosaccharides by DC-SIGN and DC-SIGNR. Science 294(5549), 2163-6.
  146. Heinz, F. X., Stiasny, K., Puschner-Auer, G., Holzmann, H., Allison, S. L., Mandl, C. W., and Kunz, C. (1994). Structural changes and functional control of the tick-borne encephalitis virus glycoprotein E by the heterodimeric association with protein prM. Virology 198(1), 109-17.
  147. Ruigrok, R. W., Schoehn, G., Dessen, A., Forest, E., Volchkov, V., Dolnik, O., Klenk, H. D., and Weissenhorn, W. (2000). Structural characterization and membrane binding properties of the matrix protein VP40 of Ebola virus. J Mol Biol 300(1), 103-12.
  148. Timmins, J., Ruigrok, R. W., and Weissenhorn, W. (2004). Structural studies on the Ebola virus matrix protein VP40 indicate that matrix proteins of enveloped RNA viruses are analogues but not homologues. FEMS Microbiol Lett 233(2), 179-86.
  149. Fouillot-Coriou, N., and Roux, L. (2000). Structure-function analysis of the Sendai virus F and HN cytoplasmic domain: different role for the two proteins in the production of virus particle. Virology 270(2), 464-75.
  150. Swanepoel, R., Smit, S. B., Rollin, P. E., Formenty, P., Leman, P. A., Kemp, A., Burt, F. J., Grobbelaar, A. A., Croft, J., Bausch, D. G., Zeller, H., Leirs, H., Braack, L. E., Libande, M. L., Zaki, S., Nichol, S. T., Ksiazek, T. G., and Paweska, J. T. (2007). Studies of reservoir hosts for Marburg virus. Emerg Infect Dis 13(12), 1847-51.
  151. Muhlberger, E., Trommer, S., Funke, C., Volchkov, V., Klenk, H. D., and Becker, S. (1996). Termini of all mRNA species of Marburg virus: sequence and secondary structure. Virology 223(2), 376-80.
  152. Huang, Y., Xu, L., Sun, Y., and Nabel, G. J. (2002). The assembly of Ebola virus nucleocapsid requires virion-associated proteins 35 and 24 and posttranslational modification of nucleoprotein. Mol Cell 10(2), 307-16.
  153. Dominguez-Soto, A., Aragoneses-Fenoll, L., Martin-Gayo, E., Martinez-Prats, L., Colmenares, M., Naranjo-Gomez, M., Borras, F. E., Munoz, P., Zubiaur, M., Toribio, M. L., Delgado, R., and Corbi, A. L. (2007). The DC-SIGN-related lectin LSECtin mediates antigen capture and pathogen binding by human myeloid cells. Blood 109(12), 5337-45.
  154. Higashi, N., Fujioka, K., Denda-Nagai, K., Hashimoto, S., Nagai, S., Sato, T., Fujita, Y., Morikawa, A., Tsuiji, M., Miyata-Takeuchi, M., Sano, Y., Suzuki, N., Yamamoto, K., Matsushima, K., and Irimura, T. (2002). The macrophage C-type lectin specific for galactose/N-acetylgalactosamine is an endocytic receptor expressed on monocyte- derived immature dendritic cells. J Biol Chem 277(23), 20686-93.
  155. Sanger, C., Muhlberger, E., Lotfering, B., Klenk, H. D., and Becker, S. (2002). The Marburg virus surface protein GP is phosphorylated at its ectodomain. Virology 295(1), 20-9.
  156. Kolesnikova, L., Bamberg, S., Berghofer, B., and Becker, S. (2004a). The matrix protein of Marburg virus is transported to the plasma membrane along cellular membranes: exploiting the retrograde late endosomal pathway. J Virol 78(5), 2382-93.
  157. Lotfering, B., Muhlberger, E., Tamura, T., Klenk, H. D., and Becker, S. (1999). The nucleoprotein of Marburg virus is target for multiple cellular kinases. Virology 255(1), 50- 62.
  158. Muhlberger, E., Sanchez, A., Randolf, A., Will, C., Kiley, M. P., Klenk, H. D., and Feldmann, H. (1992). The nucleotide sequence of the L gene of Marburg virus, a filovirus: homologies with paramyxoviruses and rhabdoviruses. Virology 187(2), 534-47.
  159. Rippey, J. J., Schepers, N. J., and Gear, J. H. (1984). The pathology of Marburg virus disease. S Afr Med J 66(2), 50-4.
  160. Mar'iankova, R. F., Glushakova, S. E., Pyzhik, E. V., and Lukashevich, I. S. (1993). [The penetration of the Marburg virus into eukaryotic cells]. Vopr Virusol 38(2), 74-6.
  161. Feldmann, H., Jones, S. M., Schnittler, H. J., and Geisbert, T. (2005). Therapy and prophylaxis of Ebola virus infections. Curr Opin Investig Drugs 6(8), 823-30.
  162. Whittaker, G., Bui, M., and Helenius, A. (1996). The role of nuclear import and export in influenza virus infection. Trends Cell Biol 6(2), 67-71.
  163. Muhlberger, E., Lotfering, B., Klenk, H. D., and Becker, S. (1998). Three of the four nucleocapsid proteins of Marburg virus, NP, VP35, and L, are sufficient to mediate replication and transcription of Marburg virus-specific monocistronic minigenomes. J Virol 72(11), 8756-64.
  164. Geisbert, T. W., Hensley, L. E., Jahrling, P. B., Larsen, T., Geisbert, J. B., Paragas, J., Young, H. A., Fredeking, T. M., Rote, W. E., and Vlasuk, G. P. (2003a). Treatment of Ebola virus infection with a recombinant inhibitor of factor VIIa/tissue factor: a study in rhesus monkeys. Lancet 362(9400), 1953-8.
  165. Hartlieb, B. (2006). Untersuchungen zur Funktion des Ebola-Virus-VP30 im Nukleokapsidkomplex basierend auf der Röntgenstrukturanalyse des VP30-C-Terminus. Dissertation.
  166. Timmins, J., Scianimanico, S., Schoehn, G., and Weissenhorn, W. (2001). Vesicular release of ebola virus matrix protein VP40. Virology 283(1), 1-6.
  167. Zaki, S. R., Peters, C.J. (1997). Viral Haemorrhagic Fever. Diagnostic Pathology of Infectious Diseases Appleton and Lange, Stanford, USA, 347-364.
  168. Mercer, J., and Helenius, A. (2009). Virus entry by macropinocytosis. Nat Cell Biol 11(5), 510-20.
  169. van Regenmortel, M. H., Mayo, M. A., Fauquet, C. M., and Maniloff, J. (2000). Virus nomenclature: consensus versus chaos. Arch Virol 145(10), 2227-32.
  170. McCarthy, S. E., Johnson, R. F., Zhang, Y. A., Sunyer, J. O., and Harty, R. N. (2007). Role for amino acids 212KLR214 of Ebola virus VP40 in assembly and budding. J Virol 81(20), 11452-60.
  171. Gonzalez, J. P., Herbreteau, V., Morvan, J., and Leroy, E. M. (2005). Ebola virus circulation in Africa: a balance between clinical expression and epidemiological silence. Bull Soc Pathol Exot 98(3), 210-7.
  172. Geisbert, T. W., and Hensley, L. E. (2004). Ebola virus: new insights into disease aetiopathology and possible therapeutic interventions. Expert Rev Mol Med 6(20), 1-24.
  173. Virus-like particles exhibit potential as a pan-filovirus vaccine for both Ebola and Marburg viral infections. Vaccine 23(23), 3033-42.
  174. Jones, S. M., Feldmann, H., Stroher, U., Geisbert, J. B., Fernando, L., Grolla, A., Klenk, H. D., Sullivan, N. J., Volchkov, V. E., Fritz, E. A., Daddario, K. M., Hensley, L. E., Jahrling, P. B., and Geisbert, T. W. (2005). Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses. Nat Med 11(7), 786-90.
  175. Kuhn, J. H., Radoshitzky, S. R., Guth, A. C., Warfield, K. L., Li, W., Vincent, M. J., Towner, J. S., Nichol, S. T., Bavari, S., Choe, H., Aman, M. J., and Farzan, M. (2006). Conserved receptor-binding domains of Lake Victoria marburgvirus and Zaire ebolavirus bind a common receptor. J Biol Chem 281(23), 15951-8.
  176. Reed, D. S., and Mohamadzadeh, M. (2007). Status and challenges of filovirus vaccines. Vaccine 25(11), 1923-34.
  177. Swenson, D. L., Warfield, K. L., Larsen, T., Alves, D. A., Coberley, S. S., and Bavari, S. (2008b). Monovalent virus-like particle vaccine protects guinea pigs and nonhuman primates against infection with multiple Marburg viruses. Expert Rev Vaccines 7(4), 417- 29.
  178. Watanabe, S., Takada, A., Watanabe, T., Ito, H., Kida, H., and Kawaoka, Y. (2000). Functional importance of the coiled-coil of the Ebola virus glycoprotein. J Virol 74(21), 10194-201.
  179. Wagner, R., Herwig, A., Azzouz, N., and Klenk, H. D. (2005). Acylation-mediated membrane anchoring of avian influenza virus hemagglutinin is essential for fusion pore formation and virus infectivity. J Virol 79(10), 6449-58.
  180. Sanchez, A., Yang, Z. Y., Xu, L., Nabel, G. J., Crews, T., and Peters, C. J. (1998). Biochemical analysis of the secreted and virion glycoproteins of Ebola virus. J Virol 72(8), 6442-7.
  181. Kolesnikova, L., Muhlberger, E., Ryabchikova, E., and Becker, S. (2000). Ultrastructural organization of recombinant Marburg virus nucleoprotein: comparison with Marburg virus inclusions. J Virol 74(8), 3899-904.
  182. Schmitt, A. P., He, B., and Lamb, R. A. (1999). Involvement of the cytoplasmic domain of the hemagglutinin-neuraminidase protein in assembly of the paramyxovirus simian virus 5. J Virol 73(10), 8703-12.
  183. Ito, H., Watanabe, S., Takada, A., and Kawaoka, Y. (2001). Ebola virus glycoprotein: proteolytic processing, acylation, cell tropism, and detection of neutralizing antibodies. J Virol 75(3), 1576-80.
  184. Stroher, U., West, E., Bugany, H., Klenk, H. D., Schnittler, H. J., and Feldmann, H. (2001). Infection and activation of monocytes by Marburg and Ebola viruses. J Virol 75(22), 11025-33.
  185. Jasenosky, L. D., Neumann, G., Lukashevich, I., and Kawaoka, Y. (2001). Ebola virus VP40-induced particle formation and association with the lipid bilayer. J Virol 75(11), 5205-14.
  186. Dutch, R. E., and Lamb, R. A. (2001). Deletion of the cytoplasmic tail of the fusion protein of the paramyxovirus simian virus 5 affects fusion pore enlargement. J Virol 75(11), 5363-9.
  187. Membrane-permeable luciferin esters for assay of firefly luciferase in live intact cells. Biochem J 276 ( Pt 3), 637-41.
  188. Schnell, M. J., Buonocore, L., Boritz, E., Ghosh, H. P., Chernish, R., and Rose, J. K. (1998). Requirement for a non-specific glycoprotein cytoplasmic domain sequence to drive efficient budding of vesicular stomatitis virus. Embo J 17(5), 1289-96.
  189. Neumann, G., Ebihara, H., Takada, A., Noda, T., Kobasa, D., Jasenosky, L. D., Watanabe, S., Kim, J. H., Feldmann, H., and Kawaoka, Y. (2005). Ebola virus VP40 late domains are not essential for viral replication in cell culture. J Virol 79(16), 10300-7.
  190. Weik, M., Enterlein, S., Schlenz, K., and Muhlberger, E. (2005). The Ebola virus genomic replication promoter is bipartite and follows the rule of six. J Virol 79(16), 10660-71.
  191. Wahl-Jensen, V. M., Afanasieva, T. A., Seebach, J., Stroher, U., Feldmann, H., and Schnittler, H. J. (2005). Effects of Ebola virus glycoproteins on endothelial cell activation and barrier function. J Virol 79(16), 10442-50.
  192. Yang, X., Kurteva, S., Ren, X., Lee, S., and Sodroski, J. (2005). Stoichiometry of envelope glycoprotein trimers in the entry of human immunodeficiency virus type 1. J Virol 79(19), 12132-47.
  193. Cathomen, T., Naim, H. Y., and Cattaneo, R. (1998). Measles viruses with altered envelope protein cytoplasmic tails gain cell fusion competence. J Virol 72(2), 1224-34.
  194. Han, Z., and Harty, R. N. (2005). Packaging of actin into Ebola virus VLPs. Virol J 2, 92.
  195. Enterlein, S., Volchkov, V., Weik, M., Kolesnikova, L., Volchkova, V., Klenk, H. D., and Muhlberger, E. (2006). Rescue of recombinant Marburg virus from cDNA is dependent on nucleocapsid protein VP30. J Virol 80(2), 1038-43.
  196. Neumann, G., Feldmann, H., Watanabe, S., Lukashevich, I., and Kawaoka, Y. (2002). Reverse genetics demonstrates that proteolytic processing of the Ebola virus glycoprotein is not essential for replication in cell culture. J Virol 76(1), 406-10.
  197. Kolesnikova, L., Bugany, H., Klenk, H. D., and Becker, S. (2002). VP40, the matrix protein of Marburg virus, is associated with membranes of the late endosomal compartment. J Virol 76(4), 1825-38.
  198. Waning, D. L., Schmitt, A. P., Leser, G. P., and Lamb, R. A. (2002). Roles for the cytoplasmic tails of the fusion and hemagglutinin-neuraminidase proteins in budding of the paramyxovirus simian virus 5. J Virol 76(18), 9284-97.
  199. Rao, M., Bray, M., Alving, C. R., Jahrling, P., and Matyas, G. R. (2002). 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 76(18), 9176-85.
  200. Han, Z., Boshra, H., Sunyer, J. O., Zwiers, S. H., Paragas, J., and Harty, R. N. (2003). Biochemical and functional characterization of the Ebola virus VP24 protein: implications for a role in virus assembly and budding. J Virol 77(3), 1793-800.
  201. Role of endosomal cathepsins in entry mediated by the Ebola virus glycoprotein. J Virol 80(8), 4174-8.
  202. Sullivan, N. J., Geisbert, T. W., Geisbert, J. B., Shedlock, D. J., Xu, L., Lamoreaux, L., Custers, J. H., Popernack, P. M., Yang, Z. Y., Pau, M. G., Roederer, M., Koup, R. A., Goudsmit, J., Jahrling, P. B., and Nabel, G. J. (2006). Immune protection of nonhuman primates against Ebola virus with single low-dose adenovirus vectors encoding modified GPs. PLoS Med 3(6), e177.
  203. Towner, J. S., Khristova, M. L., Sealy, T. K., Vincent, M. J., Erickson, B. R., Bawiec, D. A., Hartman, A. L., Comer, J. A., Zaki, S. R., Stroher, U., Gomes da Silva, F., del Castillo, F., Rollin, P. E., Ksiazek, T. G., and Nichol, S. T. (2006). Marburgvirus genomics and association with a large hemorrhagic fever outbreak in Angola. J Virol 80(13), 6497-516.
  204. Sinn, P. L., Hickey, M. A., Staber, P. D., Dylla, D. E., Jeffers, S. A., Davidson, B. L., Sanders, D. A., and McCray, P. B., Jr. (2003). Lentivirus vectors pseudotyped with filoviral envelope glycoproteins transduce airway epithelia from the apical surface independently of folate receptor alpha. J Virol 77(10), 5902-10.
  205. Noda, T., Ebihara, H., Muramoto, Y., Fujii, K., Takada, A., Sagara, H., Kim, J. H., Kida, H., Feldmann, H., and Kawaoka, Y. (2006). Assembly and budding of Ebolavirus. PLoS Pathog 2(9), e99.
  206. Shimojima, M., Takada, A., Ebihara, H., Neumann, G., Fujioka, K., Irimura, T., Jones, S., Feldmann, H., and Kawaoka, Y. (2006). Tyro3 family-mediated cell entry of Ebola and Marburg viruses. J Virol 80(20), 10109-16.
  207. A., Bray, M., Fritz, E. A., Fernando, L., Feldmann, F., Hensley, L. E., and Geisbert, T. W. (2007). Effective post-exposure treatment of Ebola infection. PLoS Pathog 3(1), e2.
  208. Mittler, E., Kolesnikova, L., Strecker, T., Garten, W., and Becker, S. (2007). Role of the transmembrane domain of marburg virus surface protein GP in assembly of the viral envelope. J Virol 81(8), 3942-8.
  209. Frey, S., Marsh, M., Gunther, S., Pelchen-Matthews, A., Stephens, P., Ortlepp, S., and Stegmann, T. (1995). Temperature dependence of cell-cell fusion induced by the envelope glycoprotein of human immunodeficiency virus type 1. J Virol 69(3), 1462-72.
  210. Mitnaul, L. J., Castrucci, M. R., Murti, K. G., and Kawaoka, Y. (1996). The cytoplasmic tail of influenza A virus neuraminidase (NA) affects NA incorporation into virions, virion morphology, and virulence in mice but is not essential for virus replication. J Virol 70(2), 873-9.
  211. Urata, S., Noda, T., Kawaoka, Y., Morikawa, S., Yokosawa, H., and Yasuda, J. (2007). Interaction of Tsg101 with Marburg virus VP40 depends on the PPPY motif, but not the PT/SAP motif as in the case of Ebola virus, and Tsg101 plays a critical role in the budding of Marburg virus-like particles induced by VP40, NP, and GP. J Virol 81(9), 4895-9.
  212. John, S. P., Wang, T., Steffen, S., Longhi, S., Schmaljohn, C. S., and Jonsson, C. B. (2007). Ebola virus VP30 is an RNA binding protein. J Virol 81(17), 8967-76.
  213. Volchkov, V. E., Feldmann, H., Volchkova, V. A., and Klenk, H. D. (1998). Processing of the Ebola virus glycoprotein by the proprotein convertase furin. Proc Natl Acad Sci U S A 95(10), 5762-7.
  214. Danieli, T., Pelletier, S. L., Henis, Y. I., and White, J. M. (1996). Membrane fusion mediated by the influenza virus hemagglutinin requires the concerted action of at least three hemagglutinin trimers. J Cell Biol 133(3), 559-69.
  215. Reid, S. P., Valmas, C., Martinez, O., Sanchez, F. M., and Basler, C. F. (2007). Ebola virus VP24 proteins inhibit the interaction of NPI-1 subfamily karyopherin alpha proteins with activated STAT1. J Virol 81(24), 13469-77.
  216. Kaletsky, R. L., Simmons, G., and Bates, P. (2007). Proteolysis of the Ebola virus glycoproteins enhances virus binding and infectivity. J Virol 81(24), 13378-84.
  217. Hartman, A. L., Bird, B. H., Towner, J. S., Antoniadou, Z. A., Zaki, S. R., and Nichol, S. T. (2008). Inhibition of IRF-3 activation by VP35 is critical for the high level of virulence of ebola virus. J Virol 82(6), 2699-704.
  218. Swenson, D. L., Wang, D., Luo, M., Warfield, K. L., Woraratanadharm, J., Holman, D. H., Dong, J. Y., and Pratt, W. D. (2008a). Vaccine to confer to nonhuman primates complete protection against multistrain Ebola and Marburg virus infections. Clin Vaccine Immunol 15(3), 460-7.
  219. Yamayoshi, S., Noda, T., Ebihara, H., Goto, H., Morikawa, Y., Lukashevich, I. S., Neumann, G., Feldmann, H., and Kawaoka, Y. (2008). Ebola virus matrix protein VP40 uses the COPII transport system for its intracellular transport. Cell Host Microbe 3(3), 168-77.
  220. Spies, C. P., Ritter, G. D., Jr., Mulligan, M. J., and Compans, R. W. (1994). Truncation of the cytoplasmic domain of the simian immunodeficiency virus envelope glycoprotein alters the conformation of the external domain. J Virol 68(2), 585-91.
  221. Conformational changes induced in the envelope glycoproteins of the human and simian immunodeficiency viruses by soluble receptor binding. J Virol 67(12), 7383-93.
  222. Geisbert, T. W., Daddario-DiCaprio, K. M., Williams, K. J., Geisbert, J. B., Leung, A., Feldmann, F., Hensley, L. E., Feldmann, H., and Jones, S. M. (2008c). Recombinant vesicular stomatitis virus vector mediates postexposure protection against Sudan Ebola hemorrhagic fever in nonhuman primates. J Virol 82(11), 5664-8.
  223. Simpson, D. A., and Lamb, R. A. (1992). Alterations to influenza virus hemagglutinin cytoplasmic tail modulate virus infectivity. J Virol 66(2), 790-803.
  224. Phosphoinositide-3 kinase-Akt pathway controls cellular entry of Ebola virus. PLoS Pathog 4(8), e1000141.
  225. Harrison, S. C. (2008). Viral membrane fusion. Nat Struct Mol Biol 15(7), 690-8.
  226. Towner, J. S., Sealy, T. K., Khristova, M. L., Albarino, C. G., Conlan, S., Reeder, S. A., Quan, P. L., Lipkin, W. I., Downing, R., Tappero, J. W., Okware, S., Lutwama, J., Bakamutumaho, B., Kayiwa, J., Comer, J. A., Rollin, P. E., Ksiazek, T. G., and Nichol, S. T. (2008). Newly discovered ebola virus associated with hemorrhagic fever outbreak in Uganda. PLoS Pathog 4(11), e1000212.
  227. Geisbert, T. W., Daddario-Dicaprio, K. M., Lewis, M. G., Geisbert, J. B., Grolla, A., Leung, A., Paragas, J., Matthias, L., Smith, M. A., Jones, S. M., Hensley, L. E., Feldmann, H., and Jahrling, P. B. (2008b). Vesicular stomatitis virus-based ebola vaccine is well- tolerated and protects immunocompromised nonhuman primates. PLoS Pathog 4(11), e1000225.
  228. Ludwig, T., Theissen, S. M., Morton, M. J., and Caplan, M. J. (2008). The cytoplasmic tail dileucine motif LL572 determines the glycosylation pattern of membrane-type 1 matrix metalloproteinase. J Biol Chem 283(51), 35410-8.
  229. Magnus, C., Rusert, P., Bonhoeffer, S., Trkola, A., and Regoes, R. R. (2009). Estimating the stoichiometry of human immunodeficiency virus entry. J Virol 83(3), 1523-31.
  230. Swanepoel, R., Leman, P. A., Burt, F. J., Zachariades, N. A., Braack, L. E., Ksiazek, T. G., Rollin, P. E., Zaki, S. R., and Peters, C. J. (1996). Experimental inoculation of plants and animals with Ebola virus. Emerg Infect Dis 2(4), 321-5.
  231. Kolesnikova, L., Strecker, T., Morita, E., Zielecki, F., Mittler, E., Crump, C., and Becker, S. (2009). Vacuolar protein sorting pathway contributes to the release of Marburg virus. J Virol 83(5), 2327-37.
  232. Kaletsky, R. L., Francica, J. R., Agrawal-Gamse, C., and Bates, P. (2009). Tetherin- mediated restriction of filovirus budding is antagonized by the Ebola glycoprotein. Proc Natl Acad Sci U S A 106(8), 2886-91.
  233. Dube, D., Brecher, M. B., Delos, S. E., Rose, S. C., Park, E. W., Schornberg, K. L., Kuhn, J. H., and White, J. M. (2009). The primed ebolavirus glycoprotein (19-kilodalton GP1,2): sequence and residues critical for host cell binding. J Virol 83(7), 2883-91.
  234. Sun, Y., Carrion, R., Jr., Ye, L., Wen, Z., Ro, Y. T., Brasky, K., Ticer, A. E., Schwegler, E. E., Patterson, J. L., Compans, R. W., and Yang, C. (2009). Protection against lethal challenge by Ebola virus-like particles produced in insect cells. Virology 383(1), 12-21.
  235. Halfmann, P., Ebihara, H., Marzi, A., Hatta, Y., Watanabe, S., Suresh, M., Neumann, G., Feldmann, H., and Kawaoka, Y. (2009). Replication-deficient ebolavirus as a vaccine candidate. J Virol 83(8), 3810-5.
  236. Lee, J. E., Fusco, M. L., Hessell, A. J., Oswald, W. B., Burton, D. R., and Saphire, E. O. (2008a). Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor. Nature 454(7201), 177-82.
  237. Geisbert, T. W., Geisbert, J. B., Leung, A., Daddario-Dicaprio, K. M., Hensley, L. E., Grolla, A., and Feldmann, H. (2009). Single injection vaccine protects nonhuman primates against Marburg virus and three species of Ebola virus. J Virol.
  238. Schumann, M., Gantke, T., and Muhlberger, E. (2009). Ebola virus VP35 antagonizes PKR activity through its C-terminal interferon inhibitory domain. J Virol.
  239. Weissenhorn, W., Calder, L. J., Wharton, S. A., Skehel, J. J., and Wiley, D. C. (1998a). The central structural feature of the membrane fusion protein subunit from the Ebola virus glycoprotein is a long triple-stranded coiled coil. Proc Natl Acad Sci U S A 95(11), 6032- 6.
  240. Simmons, G., Rennekamp, A. J., Chai, N., Vandenberghe, L. H., Riley, J. L., and Bates, P. (2003b). Folate receptor alpha and caveolae are not required for Ebola virus glycoprotein-mediated viral infection. J Virol 77(24), 13433-8.
  241. Naim, H. Y., Ehler, E., and Billeter, M. A. (2000). Measles virus matrix protein specifies apical virus release and glycoprotein sorting in epithelial cells. Embo J 19(14), 3576-85.
  242. Higuchi, R., Krummel, B., and Saiki, R. K. (1988). A general method of in vitro preparation and specific mutagenesis of DNA fragments: study of protein and DNA interactions. Nucleic Acids Res 16(15), 7351-67.
  243. Vesicular stomatitis virus-based vaccines protect nonhuman primates against aerosol challenge with Ebola and Marburg viruses. Vaccine 26(52), 6894-900.
  244. Takada, A., Fujioka, K., Tsuiji, M., Morikawa, A., Higashi, N., Ebihara, H., Kobasa, D., Feldmann, H., Irimura, T., and Kawaoka, Y. (2004). Human macrophage C-type lectin specific for galactose and N-acetylgalactosamine promotes filovirus entry. J Virol 78(6), 2943-7.
  245. Watanabe, S., Watanabe, T., Noda, T., Takada, A., Feldmann, H., Jasenosky, L. D., and Kawaoka, Y. (2004). Production of novel ebola virus-like particles from cDNAs: an alternative to ebola virus generation by reverse genetics. J Virol 78(2), 999-1005.
  246. Jin, H., Leser, G. P., and Lamb, R. A. (1994). The influenza virus hemagglutinin cytoplasmic tail is not essential for virus assembly or infectivity. Embo J 13(22), 5504-15.
  247. Sanchez, A., Trappier, S. G., Mahy, B. W., Peters, C. J., and Nichol, S. T. (1996). The virion glycoproteins of Ebola viruses are encoded in two reading frames and are expressed through transcriptional editing. Proc Natl Acad Sci U S A 93(8), 3602-7.
  248. Martin-Serrano, J., Perez-Caballero, D., and Bieniasz, P. D. (2004). Context-dependent effects of L domains and ubiquitination on viral budding. J Virol 78(11), 5554-63.
  249. Waning, D. L., Russell, C. J., Jardetzky, T. S., and Lamb, R. A. (2004). Activation of a paramyxovirus fusion protein is modulated by inside-out signaling from the cytoplasmic tail. Proc Natl Acad Sci U S A 101(25), 9217-22.
  250. Kolesnikova, L., Berghofer, B., Bamberg, S., and Becker, S. (2004b). Multivesicular bodies as a platform for formation of the Marburg virus envelope. J Virol 78(22), 12277-87.
  251. Schnittler, H. J., and Feldmann, H. (1999). Molecular pathogenesis of filovirus infections: role of macrophages and endothelial cells. Curr Top Microbiol Immunol 235, 175-204.
  252. Skehel, J. J., Bayley, P. M., Brown, E. B., Martin, S. R., Waterfield, M. D., White, J. M., Wilson, I. A., and Wiley, D. C. (1982). Changes in the conformation of influenza virus hemagglutinin at the pH optimum of virus-mediated membrane fusion. Proc Natl Acad Sci U S A 79(4), 968-72.
  253. Sanger, F., and Coulson, A. R. (1975). A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase. J Mol Biol 94(3), 441-8.
  254. Jahrling, P. B., Geisbert, T. W., Dalgard, D. W., Johnson, E. D., Ksiazek, T. G., Hall, W. C., and Peters, C. J. (1990). Preliminary report: isolation of Ebola virus from monkeys imported to USA. Lancet 335(8688), 502-5.
  255. Gomis-Ruth, F. X., Dessen, A., Timmins, J., Bracher, A., Kolesnikowa, L., Becker, S., Klenk, H. D., and Weissenhorn, W. (2003). The matrix protein VP40 from Ebola virus octamerizes into pore-like structures with specific RNA binding properties. Structure 11(4), 423-33.
  256. Endosomal proteolysis of the Ebola virus glycoprotein is necessary for infection. Science 308(5728), 1643-5.
  257. Johnson, R. F., Bell, P., and Harty, R. N. (2006a). Effect of Ebola virus proteins GP, NP and VP35 on VP40 VLP morphology. Virol J 3, 31.
  258. WHO (1992). Viral haemorrhagic fever in imported monkeys. Wkly Epidemiol Rec. 67(19), 142-3.
  259. WHO (2003a). Outbreaks of Ebola haemorrhagic fever, Congo and Gabon, October 2001- July 2002. Wkly Epidemiol Rec. 78(26), 223-8.
  260. Geyer, H., Will, C., Feldmann, H., Klenk, H. D., and Geyer, R. (1992). Carbohydrate structure of Marburg virus glycoprotein. Glycobiology 2(4), 299-312.


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