Correlates of disease severity in bluetongue as a model of acute arbovirus infection.

Autor: Herder V; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom., Caporale M; Istituto Zooprofilattico Sperimentale dell' Abruzzo e Molise 'G. Caporale', Teramo, Italy., MacLean OA; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom., Pintus D; Istituto Zooprofilattico Sperimentale della Sardegna, Sassari, Italy., Huang X; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom., Nomikou K; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom., Palmalux N; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom., Nichols J; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom., Scivoli R; Istituto Zooprofilattico Sperimentale della Sardegna, Sassari, Italy., Boutell C; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom., Taggart A; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom., Allan J; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom., Malik H; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom., Ilia G; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom., Gu Q; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom., Ronchi GF; Istituto Zooprofilattico Sperimentale dell' Abruzzo e Molise 'G. Caporale', Teramo, Italy., Furnon W; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom., Zientara S; Laboratory for Animal Health, INRAE, Ecole Nationale Vétérinaire d'Alfort, ANSES, Maisons-Alfort, France., Bréard E; Laboratory for Animal Health, INRAE, Ecole Nationale Vétérinaire d'Alfort, ANSES, Maisons-Alfort, France., Antonucci D; Istituto Zooprofilattico Sperimentale dell' Abruzzo e Molise 'G. Caporale', Teramo, Italy., Capista S; Istituto Zooprofilattico Sperimentale dell' Abruzzo e Molise 'G. Caporale', Teramo, Italy., Giansante D; Istituto Zooprofilattico Sperimentale dell' Abruzzo e Molise 'G. Caporale', Teramo, Italy., Cocco A; Istituto Zooprofilattico Sperimentale dell' Abruzzo e Molise 'G. Caporale', Teramo, Italy., Mercante MT; Istituto Zooprofilattico Sperimentale dell' Abruzzo e Molise 'G. Caporale', Teramo, Italy., Di Ventura M; Istituto Zooprofilattico Sperimentale dell' Abruzzo e Molise 'G. Caporale', Teramo, Italy., Da Silva Filipe A; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom., Puggioni G; Istituto Zooprofilattico Sperimentale della Sardegna, Sassari, Italy., Sevilla N; Centro de Investigación en Sanidad Animal. Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria. Consejo Superior de Investigaciones Científicas (CISA-INIA-CSIC). Valdeolmos, Madrid, Spain., Stewart ME; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom., Ligios C; Istituto Zooprofilattico Sperimentale della Sardegna, Sassari, Italy., Palmarini M; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2024 Aug 16; Vol. 20 (8), pp. e1012466. Date of Electronic Publication: 2024 Aug 16 (Print Publication: 2024).
DOI: 10.1371/journal.ppat.1012466
Abstrakt: Most viral diseases display a variable clinical outcome due to differences in virus strain virulence and/or individual host susceptibility to infection. Understanding the biological mechanisms differentiating a viral infection displaying severe clinical manifestations from its milder forms can provide the intellectual framework toward therapies and early prognostic markers. This is especially true in arbovirus infections, where most clinical cases are present as mild febrile illness. Here, we used a naturally occurring vector-borne viral disease of ruminants, bluetongue, as an experimental system to uncover the fundamental mechanisms of virus-host interactions resulting in distinct clinical outcomes. As with most viral diseases, clinical symptoms in bluetongue can vary dramatically. We reproduced experimentally distinct clinical forms of bluetongue infection in sheep using three bluetongue virus (BTV) strains (BTV-1IT2006, BTV-1IT2013 and BTV-8FRA2017). Infected animals displayed clinical signs varying from clinically unapparent, to mild and severe disease. We collected and integrated clinical, haematological, virological, and histopathological data resulting in the analyses of 332 individual parameters from each infected and uninfected control animal. We subsequently used machine learning to select the key viral and host processes associated with disease pathogenesis. We identified and experimentally validated five different fundamental processes affecting the severity of bluetongue: (i) virus load and replication in target organs, (ii) modulation of the host type-I IFN response, (iii) pro-inflammatory responses, (iv) vascular damage, and (v) immunosuppression. Overall, we showed that an agnostic machine learning approach can be used to prioritise the different pathogenetic mechanisms affecting the disease outcome of an arbovirus infection.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Herder et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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