Filoviruses: Ebola, Marburg and Disease

Abstract

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.
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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. http://www.els.net [doi: 10.1002/9780470015902.a0002232.pub3]