characterization of the novel ebolavirus Bombali virus suggests a low pathogenic potential for humans.

B S Bodmer, A Breithaupt, M Heung, J E Brunetti, C Henkel, J Müller-Guhl, E Rodríguez, L Wendt, S L Winter, M Vallbracht, A Müller, S Römer, P Chlanda, C Muñoz-Fontela, T Hoenen, B Escudero-Pérez
Author Information
  1. B S Bodmer: Institute for Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Greifswald - Insel Riems, Germany.
  2. A Breithaupt: Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, Greifswald - Insel Riems, Germany.
  3. M Heung: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
  4. J E Brunetti: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
  5. C Henkel: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
  6. J Müller-Guhl: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
  7. E Rodríguez: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
  8. L Wendt: Institute for Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Greifswald - Insel Riems, Germany.
  9. S L Winter: Schaller Research Groups, Department of Infectious Diseases, Virology, Heidelberg University Hospital, Heidelberg, Germany.
  10. M Vallbracht: Schaller Research Groups, Department of Infectious Diseases, Virology, Heidelberg University Hospital, Heidelberg, Germany.
  11. A Müller: Institute for Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Greifswald - Insel Riems, Germany.
  12. S Römer: Institute for Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Greifswald - Insel Riems, Germany.
  13. P Chlanda: Schaller Research Groups, Department of Infectious Diseases, Virology, Heidelberg University Hospital, Heidelberg, Germany.
  14. C Muñoz-Fontela: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
  15. T Hoenen: Institute for Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Greifswald - Insel Riems, Germany. ORCID
  16. B Escudero-Pérez: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.

Abstract

Ebolaviruses cause outbreaks of haemorrhagic fever in Central and West Africa. Some members of this genus such as Ebola virus (EBOV) are highly pathogenic, with case fatality rates of up to 90%, whereas others such as Reston virus (RESTV) are apathogenic for humans. Bombali virus (BOMV) is a novel ebolavirus for which complete genome sequences were recently found in free-tailed bats, although no infectious virus could be isolated. Its pathogenic potential for humans is unknown. To address this question, we first determined whether proteins encoded by the available BOMV sequence found in were functional in assays. The correction of an apparent sequencing error in the glycoprotein based on these data then allowed us to generate infectious BOMV using reverse genetics and characterize its infection of human cells. Furthermore, we used HLA-A2-transgenic, NOD-scid-IL-2γ receptor-knockout (NSG-A2) mice reconstituted with human haematopoiesis as a model to evaluate the pathogenicity of BOMV in a human-like immune environment. These data demonstrate that not only does BOMV show a slower growth rate than EBOV , but it also shows low pathogenicity in humanized mice, comparable to previous studies using RESTV. Taken together, these findings suggest a low pathogenic potential of BOMV for humans.

Keywords

References

  1. J Virol. 2001 Jun;75(11):5205-14 [PMID: 11333902]
  2. Virology. 2001 Apr 25;283(1):1-6 [PMID: 11312656]
  3. PLoS Pathog. 2013 Jan;9(1):e1003147 [PMID: 23382680]
  4. Emerg Infect Dis. 2019 Sep;25(9): [PMID: 31310231]
  5. Western Pac Surveill Response J. 2019 Jul 05;10(3):1-8 [PMID: 32110459]
  6. mBio. 2015 Feb 19;6(2):e00137 [PMID: 25698835]
  7. Nat Rev Immunol. 2007 Jul;7(7):556-67 [PMID: 17589545]
  8. Viruses. 2019 Nov 04;11(11): [PMID: 31689981]
  9. J Clin Invest. 2015 Dec;125(12):4692-8 [PMID: 26551684]
  10. J Virol. 2014 Sep;88(18):10511-24 [PMID: 24965473]
  11. J Virol. 2016 Mar 28;90(8):3890-3901 [PMID: 26819310]
  12. Virology. 2005 Feb 5;332(1):406-17 [PMID: 15661171]
  13. PLoS Pathog. 2015 Apr 30;11(4):e1004731 [PMID: 25928849]
  14. Front Immunol. 2022 Jan 05;12:694105 [PMID: 35069519]
  15. Curr Top Microbiol Immunol. 2017;411:141-169 [PMID: 28653186]
  16. Antiviral Res. 2021 Aug;192:105120 [PMID: 34126139]
  17. J Infect Dis. 2017 Dec 27;217(1):58-63 [PMID: 29087482]
  18. J Infect Dis. 2015 Oct 1;212 Suppl 2:S129-37 [PMID: 25810440]
  19. J Struct Biol. 2017 Feb;197(2):102-113 [PMID: 27444392]
  20. J Infect Dis. 2016 Mar 1;213(5):703-11 [PMID: 26582961]
  21. J Clin Invest. 2015 Dec;125(12):4421-8 [PMID: 26551677]
  22. J Virol. 2017 May 12;91(11): [PMID: 28331091]
  23. PLoS Pathog. 2012;8(8):e1002847 [PMID: 22876185]
  24. J Virol. 2006 Jul;80(13):6430-40 [PMID: 16775331]
  25. J Virol. 1999 Mar;73(3):2333-42 [PMID: 9971816]
  26. J Gen Virol. 2019 May;100(5):760-772 [PMID: 31017565]
  27. Microorganisms. 2020 Aug 11;8(8): [PMID: 32796523]
  28. Nat Rev Dis Primers. 2020 Feb 20;6(1):13 [PMID: 32080199]
  29. ILAR J. 2018 Dec 1;59(1):13-17 [PMID: 30715381]
  30. Curr Top Microbiol Immunol. 2017;411:421-445 [PMID: 28918537]
  31. J Virol. 2002 May;76(10):4855-65 [PMID: 11967302]
  32. Curr Top Microbiol Immunol. 2017;411:63-92 [PMID: 29071473]
  33. JCI Insight. 2019 Nov 1;4(21): [PMID: 31550241]
  34. J Virol. 2010 Mar;84(6):3004-15 [PMID: 20071589]
  35. Emerg Infect Dis. 2019 May;25(5):955-957 [PMID: 31002301]
  36. J Virol. 2017 Jan 31;91(4): [PMID: 27974555]
  37. J Gen Virol. 2011 Dec;92(Pt 12):2900-2905 [PMID: 21900424]
  38. J Struct Biol. 2021 Jun;213(2):107742 [PMID: 33971285]
  39. Elife. 2020 Oct 05;9: [PMID: 33016878]
  40. Nat Microbiol. 2018 Oct;3(10):1084-1089 [PMID: 30150734]
  41. J Virol. 2015 Apr;89(8):4700-4 [PMID: 25673711]
  42. Future Virol. 2009;4(6):621-635 [PMID: 20198110]
  43. J Infect Dis. 2007 Nov 15;196 Suppl 2:S142-7 [PMID: 17940942]
  44. Antiviral Res. 2019 Oct;170:104569 [PMID: 31356830]
  45. N Engl J Med. 2014 Nov 27;371(22):2092-100 [PMID: 25353969]
  46. Curr Top Microbiol Immunol. 2017;411:195-227 [PMID: 28653189]

MeSH Term

Humans
Animals
Mice
Ebolavirus
Hemorrhagic Fever, Ebola
Mice, Inbred NOD
Animals, Genetically Modified
Africa, Western

Word Cloud

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