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Tumour Necrosis Factor-α, Chemokines, and Leukocyte Infiltrate Are Biomarkers for Pathology in the Brains of Venezuelan Equine Encephalitis (VEEV)-Infected Mice.
Phelps, Amanda L; Salguero, Francisco J; Hunter, Laura; Stoll, Alexander L; Jenner, Dominic C; O'Brien, Lyn M; Williamson, E Diane; Lever, M Stephen; Laws, Thomas R.
Afiliación
  • Phelps AL; Defence Science and Technology Laboratory, Salisbury SP4 0JQ, UK.
  • Salguero FJ; UK Health Security Agency, Salisbury SP4 0JG, UK.
  • Hunter L; UK Health Security Agency, Salisbury SP4 0JG, UK.
  • Stoll AL; Defence Science and Technology Laboratory, Salisbury SP4 0JQ, UK.
  • Jenner DC; Defence Science and Technology Laboratory, Salisbury SP4 0JQ, UK.
  • O'Brien LM; Defence Science and Technology Laboratory, Salisbury SP4 0JQ, UK.
  • Williamson ED; Defence Science and Technology Laboratory, Salisbury SP4 0JQ, UK.
  • Lever MS; Defence Science and Technology Laboratory, Salisbury SP4 0JQ, UK.
  • Laws TR; Defence Science and Technology Laboratory, Salisbury SP4 0JQ, UK.
Viruses ; 15(6)2023 05 31.
Article en En | MEDLINE | ID: mdl-37376607
Venezuelan equine encephalitis virus (VEEV) is a disease typically confined to South and Central America, whereby human disease is characterised by a transient systemic infection and occasionally severe encephalitis, which is associated with lethality. Using an established mouse model of VEEV infection, the encephalitic aspects of the disease were analysed to identify biomarkers associated with inflammation. Sequential sampling of lethally challenged mice (infected subcutaneously) confirmed a rapid onset systemic infection with subsequent spread to the brain within 24 h of the challenge. Changes in inflammatory biomarkers (TNF-α, CCL-2, and CCL-5) and CD45+ cell counts were found to correlate strongly to pathology (R>0.9) and present previously unproven biomarkers for disease severity in the model, more so than viral titre. The greatest level of pathology was observed within the olfactory bulb and midbrain/thalamus. The virus was distributed throughout the brain/encephalon, often in areas not associated with pathology. The principal component analysis identified five principal factors across two independent experiments, with the first two describing almost half of the data: (1) confirmation of a systemic Th1-biased inflammatory response to VEEV infection, and (2) a clear correlation between specific inflammation of the brain and clinical signs of disease. Targeting strongly associated biomarkers of deleterious inflammation may ameliorate or even eliminate the encephalitic syndrome of this disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Virus de la Encefalitis Equina Venezolana / Encefalomielitis Equina Venezolana Tipo de estudio: Prognostic_studies Límite: Animals / Humans País/Región como asunto: America do sul / Venezuela Idioma: En Revista: Viruses Año: 2023 Tipo del documento: Article Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Virus de la Encefalitis Equina Venezolana / Encefalomielitis Equina Venezolana Tipo de estudio: Prognostic_studies Límite: Animals / Humans País/Región como asunto: America do sul / Venezuela Idioma: En Revista: Viruses Año: 2023 Tipo del documento: Article Pais de publicación: Suiza