Filoviruses: Ebola, Marburg and Disease


Ebola‐ and marburgviruses belong to the family of filoviruses and cause severe haemorrhagic fevers in humans and nonhuman primates. Since their discovery in 1967, during outbreaks in Germany and former Yugoslavia originating with nonhuman primates imported from Uganda, they have been responsible for numerous disease outbreaks in Africa, including that of unprecedented size, which is currently ongoing in West Africa. Filoviruses have also been implicated in massive die‐offs of great apes, and in recent years there have been several cases of imported infections into Europe and North America. Filoviral haemorrhagic fevers are severe diseases with case fatality rates of up to 90%. Currently, there is neither a licensed vaccine nor a specific therapy available, although experimental vaccines and treatments have shown promise in nonhuman primates, and are now being vigorously pursued in human clinical trials.

Key Concepts

  • Human pathogenic filoviruses (Ebola virus (EBOV), Sudan virus (SUDV), Taï Forest virus (TAFV), Bundibugyo virus (BDBV) and Marburg virus (MARV)) are found in Africa, primarily in bats and nonhuman primates. In contrast, Reston virus (RESTV), which is nonpathogenic in humans, originates in the Philippines, where it is found in both nonhuman primates and pigs.
  • Imported nonhuman primates have been the cause of outbreaks of filoviral haemorrhagic fever in Europe and North America, both among humans and nonhuman primates. Tourism and the return of medical aid workers have also resulted in several imported infections during the last years.
  • Bats represent the most likely reservoir for filoviruses.
  • The recent outbreak in West Africa has been responsible for over 27 000 cases (as of 27 May 2015) and is still ongoing; highlighting the threat that filovirus infection continues to pose to human health.
  • While the absolute number of filoviral haemorrhagic fever cases remain low compared to other diseases, the severe disease picture and high case fatality rates have led to a high public profile of filoviral haemorrhagic fevers.
  • The pathophysiology of filoviral haemorrhagic fevers involves vascular dysfunction, impairment of the immune system and massive dysregulation of cytokine production.
  • Death is caused by multiple organ failure as result of a syndrome resembling septic shock.
  • Currently, the only measures to combat filovirus infections are supportive therapy and patient isolation. However, basic public health measures are very effective at controlling outbreaks, when consistently and rigorously implemented.
  • Experimental treatments and vaccines in nonhuman primates exist, but are not yet licensed for use in humans. However, public interest in the current West African EBOV outbreak has accelerated efforts to see several of the more advanced therapeutic and vaccination approaches licenced.

Keywords: Ebola; Marburg; Filovirus; haemorrhagic fever

Figure 1. Genome organisation of filoviruses. Genes encoding RNP proteins (red), matrix proteins (yellow) and glycoproteins (blue) are shown, and names are indicated within their respective genes. Untranslated regions (grey) and intergenic regions (black lines) are also indicated. Gene overlaps are indicated as black arrows, and the editing site in the EBOV GP gene is marked with a blue star. The asterisk indicates the lack of transcriptional start/stop sequences between the VP24 and L genes, leading to formation of a bicistronic mRNA. Ebola virus (EBOV); Sudan virus (SUDV); Taï Forest virus (TAFV); Bundibugyo virus (BDBV); Reston virus (RESTV); Lloviu virus (LLOV). Marburg virus (MARV).
Figure 2. Geographical distribution of (a) Ebola viruses and (b) Marburg virus. Countries where Ebola virus or Marburg virus are endemic and outbreaks have been reported are indicated in red. Where endemicity is suspected but not definitively shown, the country is indicated in pink. Countries with imported cases are shown in orange.
Figure 3. Model of filovirus pathogenesis. Filoviruses infect their primary target cells, macrophages and dendritic cells, and impair their function. Further, they infect endothelial cells and parenchymal cells leading to direct tissue damage and, in conjunction with proinflammatory cytokines released by infected macrophages, lead to a loss of endothelial barrier function. Tissue factor is expressed leading to disseminated intravascular coagulation, which together with the direct tissue damage is responsible for multiorgan failure and results in a syndrome resembling septic shock.


Aleksandrowicz P , Wolf K , Falzarano D , et al. (2008) Viral haemorrhagic fever and vascular alterations. Hämostaseologie 28: 77–84.

Amman BR , Carroll SA , Reed ZD , et al. (2012) Seasonal pulses of Marburg virus circulation in juvenile Rousettus aegyptiacus bats coincide with periods of increased risk of human infection. PLoS Pathogens 8: e1002877.

Baize S , Pannetier D , Oestereich L , et al. (2014) Emergence of Zaire Ebola virus disease in Guinea. The New England Journal of Medicine 371: 1418–1425.

Basler CF and Amarasinghe GK (2009) Evasion of interferon responses by Ebola and Marburg viruses. Journal of Interferon and Cytokine Research 29: 511–520.

Bausch DG , Nichol ST , Muyembe‐Tamfum JJ , et al. (2006) Marburg hemorrhagic fever associated with multiple genetic lineages of virus. The New England Journal of Medicine 355: 909–919.

Becker S , Spiess M and Klenk HD (1995) The asialoglycoprotein receptor is a potential liver‐specific receptor for Marburg virus. The Journal of General Virology 76 (Pt 2): 393–399.

Becker S , Feldmann H , Will C and Slenczka W (1992) Evidence for occurrence of filovirus antibodies in humans and imported monkeys: do subclinical filovirus infections occur worldwide? Medical Microbiology and Immunology (Berl) 181: 43–55.

Beniac DR , Melito PL , Devarennes SL , et al. (2012) The organisation of Ebola virus reveals a capacity for extensive, modular polyploidy. PLoS One 7: e29608.

Bharat TA , Noda T , Riches JD , et al. (2012) Structural dissection of Ebola virus and its assembly determinants using cryo‐electron tomography. Proceedings of the National Academy of Sciences of the United States of America 109: 4275–4280.

Carette JE , Raaben M , Wong AC , et al. (2011) Ebola virus entry requires the cholesterol transporter Niemann‐Pick C1. Nature 477: 340–343.

Carroll SA , Towner JS , Sealy TK , et al. (2013) Molecular evolution of viruses of the family Filoviridae based on 97 whole‐genome sequences. Journal of Virology 87: 2608–2616.

CDC (2009) Imported case of Marburg hemorrhagic fever – Colorado, 2008. MMWR. Morbidity and Mortality Weekly Report 58: 1377–1381.

Choi JH , Jonsson‐Schmunk K , Qiu X , et al. (2014) A single dose respiratory recombinant adenovirus‐based vaccine provides long‐term protection for non‐human primates from lethal Ebola infection. Molecular Pharmaceutics.

Cote M , Misasi J , Ren T , et al. (2011) Small molecule inhibitors reveal Niemann‐Pick C1 is essential for Ebola virus infection. Nature 477: 344–348.

Dye JM , Herbert AS , Kuehne AI , et al. (2012) Postexposure antibody prophylaxis protects nonhuman primates from filovirus disease. Proceedings of the National Academy of Sciences of the United States of America 109: 5034–5039.

Falzarano D , Geisbert TW and Feldmann H (2011) Progress in filovirus vaccine development: evaluating the potential for clinical use. Expert Review of Vaccines 10: 63–77.

Feldmann H and Geisbert TW (2011) Ebola haemorrhagic fever. Lancet 377: 849–862.

Feldmann H , Jones SM , Daddario‐DiCaprio KM , et al. (2007) Effective post‐exposure treatment of Ebola infection. PLoS Pathogens 3: e2.

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. Journal of Virology 81: 182–192.

Geisbert TW , Young HA , Jahrling PB , et al. (2003a) Mechanisms underlying coagulation abnormalities in ebola hemorrhagic fever: overexpression of tissue factor in primate monocytes/macrophages is a key event. Journal of Infectious Diseases 188: 1618–1629.

Geisbert TW , Geisbert JB , Leung A , et al. (2009) Single injection vaccine protects nonhuman primates against Marburg virus and three species of Ebola virus. Journal of Virology 83: 7296–7304.

Geisbert TW , Hensley LE , Jahrling PB , et al. (2003b) Treatment of Ebola virus infection with a recombinant inhibitor of factor VIIa/tissue factor: a study in rhesus monkeys. Lancet 362: 1953–1958.

Geisbert TW , Lee AC , Robbins M , et al. (2010) Postexposure protection of non‐human primates against a lethal Ebola virus challenge with RNA interference: a proof‐of‐concept study. Lancet 375: 1896–1905.

Geisbert TW , Daddario‐Dicaprio KM , Lewis MG , et al. (2008) Vesicular stomatitis virus‐based ebola vaccine is well‐tolerated and protects immunocompromised nonhuman primates. PLoS Pathogens 4: e1000225.

Grolla A , Lucht A , Dick D , Strong JE and Feldmann H (2005) Laboratory diagnosis of Ebola and Marburg hemorrhagic fever. Bulletin de la Societe de Pathologie Exotique 98: 205–209.

Grolla A , Jones SM , Fernando L , et al. (2011) The use of a mobile laboratory unit in support of patient management and epidemiological surveillance during the 2005 Marburg outbreak in Angola. PLoS Neglected Tropical Diseases 5: e1183.

Groseth A , Feldmann H and Strong JE (2007) The ecology of Ebola virus. Trends in Microbiology 15: 408–416.

Groseth A , Charton JE , Sauerborn M , et al. (2009) The Ebola virus ribonucleoprotein complex: a novel VP30‐L interaction identified. Virus Research 140: 8–14.

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. Proceedings of the National Academy of Sciences of the United States of America 104: 624–629.

Hayman DT , Yu M , Crameri G , et al. (2012) Ebola virus antibodies in fruit bats, Ghana, West Africa. Emerging Infectious Diseases 18: 1207–1209.

Hensley LE , Stevens EL , Yan SB , et al. (2007) Recombinant human activated protein C for the postexposure treatment of Ebola hemorrhagic fever. Journal of Infectious Diseases 196 (Suppl 2): S390–399.

Hoenen T and Feldmann H (2014) Ebolavirus in West Africa, and the use of experimental therapies or vaccines. BMC Biology 12: 80.

Hoenen T , Groseth A , Falzarano D and Feldmann H (2006) Ebola virus: unravelling pathogenesis to combat a deadly disease. Trends in Molecular Medicine 12: 206–215.

Hoenen T , Jung S , Herwig A , Groseth A and Becker S (2010) Both matrix proteins of Ebola virus contribute to the regulation of viral genome replication and transcription. Virology 403: 56–66.

Jasenosky LD , Neumann G , Lukashevich I and Kawaoka Y (2001) Ebola virus VP40‐induced particle formation and association with the lipid bilayer. Journal of Virology 75: 5205–5214.

Kondratowicz AS , Lennemann NJ , Sinn PL , et al. (2011) From the cover: T‐cell immunoglobulin and mucin domain 1 (TIM‐1) is a receptor for Zaire Ebolavirus and Lake Victoria Marburgvirus. Proceedings of the National Academy of Sciences of the United States of America 108: 8426–8431.

Kuhn JH , Dodd LE , Wahl‐Jensen V , et al. (2011) Evaluation of perceived threat differences posed by filovirus variants. Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science 9: 361–371.

Kurosaki Y , Takada A , Ebihara H , et al. (2007) Rapid and simple detection of Ebola virus by reverse transcription‐loop‐mediated isothermal amplification. Journal of Virological Methods 141: 78–83.

Le Guenno B , Formenty P and Boesch C (1999) Ebola virus outbreaks in the Ivory Coast and Liberia, 1994‐1995. Current Topics in Microbiology and Immunology 235: 77–84.

Ledgerwood JE , DeZure AD , Stanley DA , et al. (2014) Chimpanzee adenovirus vector Ebola vaccine – preliminary report. The New England journal of medicine. epub ahead of print.

Leroy EM , Epelboin A , Mondonge V , et al. (2009) Human Ebola outbreak resulting from direct exposure to fruit bats in Luebo, Democratic Republic of Congo, 2007. Vector Borne and Zoonotic Diseases 9: 723–728.

Leroy EM , Kumulungui B , Pourrut X , et al. (2005) Fruit bats as reservoirs of Ebola virus. Nature 438: 575–576.

Levi M (2004) Current understanding of disseminated intravascular coagulation. British Journal of Haematology 124: 567–576.

Licata JM , Simpson‐Holley M , Wright NT , et al. (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. Journal of Virology 77: 1812–1819.

Lucht A , Formenty P , Feldmann H , et al. (2007) Development of an immunofiltration‐based antigen‐detection assay for rapid diagnosis of Ebola virus infection. Journal of Infectious Diseases 196 (Suppl 2): S184–192.

Martini GA , Knauff HG , Schmidt HA , Mayer G and Baltzer G (1968) On the hitherto unknown, in monkeys originating infectious disease: Marburg virus disease. Deutsche Medizinische Wochenschrift 93: 559–571.

Mehedi M , Falzarano D , Seebach J , et al. (2011) A new Ebola virus nonstructural glycoprotein expressed through RNA editing. Journal of Virology 85: 5406–5414.

Mehedi M , Hoenen T , Robertson S , et al. (2013) Ebola virus RNA editing depends on the primary editing site sequence and an upstream secondary structure. PLoS Pathogens 9: e1003677.

Miranda ME and Miranda NL (2011) Reston ebolavirus in humans and animals in the Philippines: a review. Journal of Infectious Diseases 204 (Suppl 3): S757–760.

Mire CE , Miller AD , Carville A , et al. (2012) Recombinant vesicular stomatitis virus vaccine vectors expressing filovirus glycoproteins lack neurovirulence in nonhuman primates. PLoS Neglected Tropical Diseases 6: e1567.

Mohan GS , Li W , Ye L , Compans RW and Yang C (2012) Antigenic subversion: a novel mechanism of host immune evasion by Ebola virus. PLoS Pathogens 8: e1003065.

Muhlberger E (2007) Filovirus replication and transcription. Future Virology 2: 205–215.

Nanbo A , Imai M , Watanabe S , et al. (2010) Ebolavirus is internalized into host cells via macropinocytosis in a viral glycoprotein‐dependent manner. PLoS Pathogens 6: e1001121.

Negredo A , Palacios G , Vazquez‐Moron S , et al. (2011) Discovery of an ebolavirus‐like filovirus in europe. PLoS Pathogens 7: e1002304.

Nidom CA , Nakayama E , Nidom RV , et al. (2012) Serological evidence of Ebola virus infection in Indonesian orangutans. PLoS One 7: e40740.

Olival KJ , Islam A , Yu M , et al. (2013) Ebola virus antibodies in fruit bats, bangladesh. Emerging Infectious Diseases 19: 270–273.

Pan Y , Zhang W , Cui L , et al. (2014) Reston virus in domestic pigs in China. Archives of Virology 159: 1129–1132.

Piot P , Bureau P , Breman G et al., (1978) Clinical Aspects of Ebola Virus infection in Yambuku area, Zaire, 1976. In: Pattyn SR (ed.) Ebola Virus Haemorrhagic Fever pp. 17–21. Amsterdam: Elsevier.

Pourrut X , Delicat A , Rollin PE , et al. (2007) Spatial and temporal patterns of Zaire ebolavirus antibody prevalence in the possible reservoir bat species. Journal of Infectious Diseases 196 (Suppl 2): S176–183.

Qiu X , Wong G , Audet J , et al. (2014) Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature 514: 47–53.

Ryan SJ and Walsh PD (2011) Consequences of non‐intervention for infectious disease in African great apes. PLoS One 6: e29030.

Smith DH , Francis DP and Simpson DIH (1978) African haemorrhagic fever in the southern sudan, 1976: The clinical manifestations. In: Pattyn SR (ed.) Ebola Virus Haemorrhagic Fever pp. 27–30. Amsterdam: Elsevier.

Stroher U and Feldmann H (2006) Progress towards the treatment of Ebola haemorrhagic fever. Expert Opinion on Investigational Drugs 15: 1523–1535.

Swenson DL , Warfield KL , Larsen T , et al. (2008a) Monovalent virus‐like particle vaccine protects guinea pigs and nonhuman primates against infection with multiple Marburg viruses. Expert Review of Vaccines 7: 417–429.

Swenson DL , Wang D , Luo M , et al. (2008b) Vaccine to confer to nonhuman primates complete protection against multistrain Ebola and Marburg virus infections. Clinical and Vaccine Immunology 15: 460–467.

Taniguchi S , Watanabe S , Masangkay JS , et al. (2011) Reston Ebolavirus antibodies in bats, the Philippines. Emerging Infectious Diseases 17: 1559–1560.

Timen A , Koopmans MP , Vossen AC , et al. (2009) Response to imported case of Marburg hemorrhagic fever, the Netherland. Emerging Infectious Diseases 15: 1171–1175.

Towner JS , Sealy TK , Khristova ML , et al. (2008) Newly discovered ebola virus associated with hemorrhagic fever outbreak in Uganda. PLoS Pathogens 4: e1000212.

Towner JS , Amman BR , Sealy TK , et al. (2009) Isolation of genetically diverse Marburg viruses from Egyptian fruit bats. PLoS Pathogens 5: e1000536.

Tuffs A (2009) Experimental vaccine may have saved Hamburg scientist from Ebola fever. BMJ 338: b1223.

Valmas C , Grosch MN , Schumann M , et al. (2010) Marburg virus evades interferon responses by a mechanism distinct from ebola virus. PLoS Pathogens 6: e1000721.

Volchkov VE , Becker S , Volchkova VA , et al. (1995) GP mRNA of Ebola virus is edited by the Ebola virus polymerase and by T7 and vaccinia virus polymerases. Virology 214: 421–430.

Wahl‐Jensen VM , Afanasieva TA , Seebach J , et al. (2005) Effects of Ebola virus glycoproteins on endothelial cell activation and barrier function. Journal of Virology 79: 10442–10450.

Warfield KL , Swenson DL , Olinger GG , et al. (2007) Ebola virus‐like particle‐based vaccine protects nonhuman primates against lethal Ebola virus challenge. Journal of Infectious Diseases 196 (Suppl 2): S430–437.

Warren TK , Warfield KL , Wells J , et al. (2010) Advanced antisense therapies for postexposure protection against lethal filovirus infections. Nature Medicine 16: 991–994.

Warren TK , Wells J , Panchal RG , et al. (2014) Protection against filovirus diseases by a novel broad‐spectrum nucleoside analogue BCX4430. Nature 508: 402–405.

Watanabe S , Noda T , Halfmann P , Jasenosky L and Kawaoka Y (2007) Ebola virus (EBOV) VP24 inhibits transcription and replication of the EBOV genome. Journal of Infectious Diseases 196 (Suppl 2): S284–290.

Watt A , Moukambi F , Banadyga L , et al. (2014) A novel life cycle modeling system for Ebola virus shows a genome length‐dependent role of VP24 in virus infectivity. Journal of Virology 88: 10511–10524.

Wong G , Audet J , Fernando L , et al. (2014) Immunization with vesicular stomatitis virus vaccine expressing the Ebola glycoprotein provides sustained long‐term protection in rodents. Vaccine 32: 5722–5729.

Yuan J , Zhang Y , Li J , et al. (2012) Serological evidence of ebolavirus infection in bats, China. Virology Journal 9: 236.

Zampieri CA , Sullivan NJ and Nabel GJ (2007) Immunopathology of highly virulent pathogens: insights from Ebola virus. Nature Immunology 8: 1159–1164.

Further Reading

Klenk H‐D and Feldmann H (2004) Ebola and Marburg Viruses: Molecular and Cellular Biology. Wymondham, United Kingdom: Horizon Bioscience.

Kuhn JH (2008) Filoviruses. Wien, Austria: Springer.

Sanchez A , Geisbert T and Feldmann H (2014) Filoviridae – Marburg and Ebola viruses. In: Knipe D (ed) Fields Virology, 6th edn, pp. 923–956. Philadelphia, PA: Lippincott Williams and Wilkins.

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Groseth, Allison, Eickmann, Markus, Ebihara, Hideki, Becker, Stephan, and Hoenen, Thomas(Jul 2015) Filoviruses: Ebola, Marburg and Disease. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0002232.pub3]