A mouse model for chikungunya: young age and inefficient type-I interferon signaling are risk factors for severe disease
Autor(es): Couderc Thérèse, Chrétien Fabrice, Schilte Clémentine, Disson Olivier, Brigitte Madly, Guivel-Benhassine Florence, Touret Yasmina, Barau Georges, Cayet Nadège,Schuffenecker Isabelle,Desprès Philippe,Arenzana-Seisdedos Fern-o,Michault Alain,Albert Matthew L,Lecuit Marc
Resumo: Chikungunya virus (CHIKV) is a re-emerging arbovirus responsible for a massive outbreak currently afflicting the Indian Ocean region - India. Infection from CHIKV typically induces a mild disease in humans, characterized by fever, myalgia, arthralgia, - rash. Cases of severe CHIKV infection involving the central nervous system (CNS) have recently been described in neonates as well as in adults with underlying conditions. The pathophysiology of CHIKV infection - the basis for disease severity are unknown. To address these critical issues, we have developed an animal model of CHIKV infection. We show here that whereas wild type (WT) adult mice are resistant to CHIKV infection, WT mouse neonates are susceptible - neonatal disease severity is age-dependent. Adult mice with a partially (IFN-alpha/betaR(+/-)) or totally (IFN-alpha/betaR(-/-)) abrogated type-I IFN pathway develop a mild or severe infection, respectively. In mice with a mild infection, after a burst of viral replication in the liver, CHIKV primarily targets muscle, joint, - skin fibroblasts, a cell - tissue tropism similar to that observed in biopsy samples of CHIKV-infected humans. In case of severe infections, CHIKV also disseminates to other tissues including the CNS, where it specifically targets the choroid plexuses - the leptomeninges. Together, these data indicate that CHIKV-associated symptoms match viral tissue - cell tropisms, - demonstrate that the fibroblast is a predominant target cell of CHIKV. These data also identify the neonatal phase - inefficient type-I IFN signaling as risk factors for severe CHIKV-associated disease. The development of a permissive small animal model will expedite the testing of future vaccines - therapeutic c-idates.
Imprenta: PLoS Pathogens, v. 4, n. 2, p. e29, 2008
Identificador do objeto digital: 10.1371/journal.ppat.0040029
Descritores: Chikungunya virus - Arbovirus ; Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Cytopathology ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Cytokines ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Public health
Data de publicação: 2008
