Elucidating variations in the nucleotide sequence of Ebola virus associated with increasing pathogenicity

Stuart D Dowall, David A Matthews, Isabel Garcia-Dorival, Irene Taylor, John Kenny, Christiane Hertz-Fowler, Neil Hall, Kara Corbin-Lickfett, Cyril Empig, Kyle Schlunegger, John N Barr, Miles W Carroll, Roger Hewson, Julian A Hiscox

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

BACKGROUND: Ebolaviruses causes a severe and often fatal hemorrhagic fever in humans, with some species such as Ebola virus having case fatality rates approaching 90%. Currently the worst Ebola virus outbreak since the disease was discovered is occurring in West Africa. Although thought to be a zoonotic infection, a concern is that with increasing numbers of humans being infected, Ebola virus variants could be selected which are better adapted for human-to-human transmission.

RESULTS: To investigate whether genetic changes in Ebola virus become established in response to adaptation in a different host, a guinea pig model of infection was used. In this experimental system, guinea pigs were infected with Ebola virus (EBOV), which initially did not cause disease. To simulate transmission to uninfected individuals, the virus was serially passaged five times in naive animals. As the virus was passaged, virulence increased and clinical effects were observed in the guinea pig. An RNAseq and consensus mapping approach was then used to evaluate potential nucleotide changes in the Ebola virus genome at each passage.

CONCLUSIONS: Upon passage in the guinea pig model, EBOV become more virulent, RNA editing and also coding changes in key proteins become established. The data suggest that the initial evolutionary trajectory of EBOV in a new host can lead to a gain in virulence. Given the circumstances of the sustained transmission of EBOV in the current outbreak in West Africa, increases in virulence may be associated with prolonged and uncontrolled epidemics of EBOV.

Original languageEnglish
Pages (from-to)540
JournalGenome Biology
Volume15
Issue number11
DOIs
Publication statusPublished - 2014

Keywords

  • Animals
  • Disease Models, Animal
  • Ebolavirus
  • Guinea Pigs
  • Hemorrhagic Fever, Ebola
  • Humans
  • RNA Editing
  • Sequence Analysis, DNA
  • Viral Proteins

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