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

ABSTRACT: 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.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.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.

SUBMITTER: Dowall SD

PROVIDER: S-EPMC4289381 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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

Dowall Stuart D SD Matthews David A DA Garcia-Dorival Isabel I Taylor Irene I Kenny John J Hertz-Fowler Christiane C Hall Neil N Corbin-Lickfett Kara K Empig Cyril C Schlunegger Kyle K Barr John N JN Carroll Miles W MW Hewson Roger R Hiscox Julian A JA

Genome biology 20140101 11

<h4>Background</h4>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.<h4>Results</ ...[more]

PMID: 25416632

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Project description:ImportanceSurvivors of Ebola virus disease (EVD) may experience ocular sequelae. Comparison with antibody-negative individuals from the local population is required to characterize the disease.ObjectiveTo assess features of ophthalmic disease specific to EVD.Design, setting, and participantsThis baseline cross-sectional analysis of survivors of EVD and their close contacts was conducted within PREVAIL III, a 5-year, longitudinal cohort study. Participants who enrolled at John F. Kennedy Medical Center in Liberia, West Africa from June 2015 to March 2016 were included in this analysis. Close contacts were defined as household members or sex partners of survivors of EVD. Data were analyzed from July 2016 to July 2020.ExposuresAll participants, both survivors and close contacts, underwent testing of IgG antibody levels against Ebola virus surface glycoprotein.Main outcomes and measuresOcular symptoms, anterior and posterior ophthalmologic examination findings, and optical coherence tomography images were compared between antibody-positive survivors and antibody-negative close contacts.ResultsA total of 564 antibody-positive survivors (320 [56.7%] female; mean [SD] age, 30.3 [14.0] years) and 635 antibody-negative close contacts (347 [54.6%] female; mean [SD] age, 25.8 [15.5] years) were enrolled in this study. Survivors were more likely to demonstrate color vision deficit (28.9% vs 19.0%, odds ratio [OR], 1.6; 95% CI, 1.2-2.1) and lower intraocular pressure (12.4 vs 13.5 mm Hg; mean difference, -1.2 mm Hg; 95% CI, -1.6 to -0.8 mm Hg) compared with close contacts. Dilated fundus examination revealed a higher percentage of vitreous cells (7.8% vs 0.5%; OR, 16.6; 95% CI, 5.0-55.2) and macular scars (4.6% vs 1.6%; OR, 2.8; 95% CI, 1.4-5.5) in survivors than in close contacts. Uveitis was present in 26.4% of survivors and 12.1% of close contacts (OR, 2.4; 95% CI, 1.8-3.2). Among all participants with uveitis, survivors were more likely than close contacts to have intermediate uveitis (34.2% vs 6.5% of all cases; OR, 7.8; 95% CI, 3.1-19.7) and had thicker mean central subfield thickness on optical coherence tomography (222 vs 212 μm; mean difference, 14.4 μm; 95% CI, 1.9-26.9 μm).Conclusions and relevanceIn this cross-sectional study, survivors of EVD had a distinct spectrum of ocular and neuro-ophthalmologic findings compared with close contacts that potentially require medical and surgical treatment.

Dataset Information

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

Publications

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

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