Usutu virus-induced meningoencephalitis in immunocompetent mice is characterized by the recruitment of mononuclear cells and a proinflammatory T helper 1 response
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Le résumé fourni par la source
ABSTRACT Usutu virus (USUV) is an arbovirus and has emerged as a potential cause of encephalitis in humans and other vertebrates. The increasing detection of USUV in mosquitoes and birds across Africa and Central Europe, along with the lack of specific treatments or vaccines for many encephalitic orthoflaviviruses, underscores the need for focused research. In this study, we developed a USUV infection model in immunocompetent C57BL/6 mice (8–12 weeks old) to characterize disease development and associated inflammatory mechanisms. Mice were intracranially infected with 10 4 PFU of USUV, leading to neurological symptoms such as hunched posture, paralysis, conjunctivitis, and eventual death by day 6 post-infection. Meningeal cell infiltration and microglia activation were most prevalent in mouse brains; however, neuronal loss was not observed at the peak of the disease, which coincided with increased viral load and leukocyte infiltration. The immune response in the brain was marked by the systematic recruitment and activation of macrophages, neutrophils, and T lymphocytes. A noticeable shift was seen in CD4+ T cells toward T helper 1 (Th1) polarization, which corroborates a massive increase in the expression of Th1-associated cytokines and chemokines at the peak of infection, indicative of an augmented proinflammatory state. Additionally, a rise in regulatory T cells was observed, peaking on day 6 post-infection. These findings highlight the dynamic nature of the host response to USUV infection, enhance our understanding of the disease pathogenesis, and address the scarcity of immunocompetent experimental models for the investigation of neglected emerging flaviviruses. IMPORTANCE Mosquito-borne viruses, including USUV, are maintained in nature through complex cycles involving arthropod vectors and vertebrate hosts. A comprehensive understanding of USUV biology and host-pathogen interactions is crucial for developing effective treatments, which necessitates reliable experimental models (G. J. Sips, J. Wilschut, and J. M. Smit, Rev Med Virol 22:69–87, 2012, https://doi.org/10.1002/rmv.712 ; T. C. Pierson and M. S. Diamond, Nat Microbiol 5:796–812, 2020, https://doi.org/10.1038/s41564-020-0714-0 ). The establishment of a USUV infection model in immunocompetent adult mice brings new perspectives on the inflammatory component of viral encephalitis, which is difficult to study in mice lacking antiviral interferon responses. Moreover, USUV is an emerging viral disease lacking therapeutic and preventive measures. The interplay of USUV pathogenesis and the host’s immune response indicates that lymphocytes and monocytes participate in USUV infection in this model and could be explored in search of treatments targeting immunopathogenic processes triggered by infection.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Usutu virus-induced meningoencephalitis in immunocompetent mice is characterized by the recruitment of mononuclear cells and a proinflammatory T helper 1 response
- Date Crossref
- 18/03/2025
- Éditeur
- American Society for Microbiology
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Universidade Estadual de Campinas (UNICAMP) pays non établi dans la noticeUniversité ou école supérieure
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Brazilian Center for Research in Energy and Materials pays non établi dans la noticeInstitution
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Brazilian Biosciences National Laboratory pays non établi dans la noticeStructure de recherche
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Morpho (United States) pays non établi dans la noticeEntreprise
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Universidade de São Paulo pays non établi dans la noticeUniversité ou école supérieure
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Rega Institute for Medical Research pays non établi dans la noticeStructure de recherche
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KU Leuven pays non établi dans la noticeUniversité ou école supérieure
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State University of Campinas Graduate Program in Genetics and Molecular Biology pays non établi dans la noticeUniversité ou école supérieure
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University of São Paulo Department of Pharmacology pays non établi dans la noticeUniversité ou école supérieure
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Laboratory of Molecular Immunology Department of Microbiology pays non établi dans la noticeStructure de recherche
Universidade Estadual de Campinas (UNICAMP), Brazilian Center for Research in Energy and Materials et Brazilian Biosciences National Laboratory, avec 7 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.