A mouse model for Chikungunya: young age and inefficient type-I interferon signaling are risk factors for severe disease.
Chikungunya virus (CHIKV) is a re-emerging arbovirus responsible for a massive outbreak currently afflicting the Indian Ocean region and India. Infection from CHIKV typically induces a mild disease in humans, characterized by fever, myalgia, arthralgia, and rash. Cases of severe CHIKV infection invo...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2008
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/1e32b6aa498f4cd1b776c683169198b3 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:1e32b6aa498f4cd1b776c683169198b3 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:1e32b6aa498f4cd1b776c683169198b32021-11-25T05:46:44ZA mouse model for Chikungunya: young age and inefficient type-I interferon signaling are risk factors for severe disease.1553-73661553-737410.1371/journal.ppat.0040029https://doaj.org/article/1e32b6aa498f4cd1b776c683169198b32008-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18282093/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Chikungunya virus (CHIKV) is a re-emerging arbovirus responsible for a massive outbreak currently afflicting the Indian Ocean region and India. Infection from CHIKV typically induces a mild disease in humans, characterized by fever, myalgia, arthralgia, and 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 and 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 and 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, and skin fibroblasts, a cell and 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 and the leptomeninges. Together, these data indicate that CHIKV-associated symptoms match viral tissue and cell tropisms, and demonstrate that the fibroblast is a predominant target cell of CHIKV. These data also identify the neonatal phase and 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 and therapeutic candidates.Thérèse CoudercFabrice ChrétienClémentine SchilteOlivier DissonMadly BrigitteFlorence Guivel-BenhassineYasmina TouretGeorges BarauNadège CayetIsabelle SchuffeneckerPhilippe DesprèsFernando Arenzana-SeisdedosAlain MichaultMatthew L AlbertMarc LecuitPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 4, Iss 2, p e29 (2008) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
| spellingShingle |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Thérèse Couderc Fabrice Chrétien Clémentine Schilte Olivier Disson Madly Brigitte Florence Guivel-Benhassine Yasmina Touret Georges Barau Nadège Cayet Isabelle Schuffenecker Philippe Desprès Fernando Arenzana-Seisdedos Alain Michault Matthew L Albert Marc Lecuit A mouse model for Chikungunya: young age and inefficient type-I interferon signaling are risk factors for severe disease. |
| description |
Chikungunya virus (CHIKV) is a re-emerging arbovirus responsible for a massive outbreak currently afflicting the Indian Ocean region and India. Infection from CHIKV typically induces a mild disease in humans, characterized by fever, myalgia, arthralgia, and 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 and 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 and 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, and skin fibroblasts, a cell and 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 and the leptomeninges. Together, these data indicate that CHIKV-associated symptoms match viral tissue and cell tropisms, and demonstrate that the fibroblast is a predominant target cell of CHIKV. These data also identify the neonatal phase and 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 and therapeutic candidates. |
| format |
article |
| author |
Thérèse Couderc Fabrice Chrétien Clémentine Schilte Olivier Disson Madly Brigitte Florence Guivel-Benhassine Yasmina Touret Georges Barau Nadège Cayet Isabelle Schuffenecker Philippe Desprès Fernando Arenzana-Seisdedos Alain Michault Matthew L Albert Marc Lecuit |
| author_facet |
Thérèse Couderc Fabrice Chrétien Clémentine Schilte Olivier Disson Madly Brigitte Florence Guivel-Benhassine Yasmina Touret Georges Barau Nadège Cayet Isabelle Schuffenecker Philippe Desprès Fernando Arenzana-Seisdedos Alain Michault Matthew L Albert Marc Lecuit |
| author_sort |
Thérèse Couderc |
| title |
A mouse model for Chikungunya: young age and inefficient type-I interferon signaling are risk factors for severe disease. |
| title_short |
A mouse model for Chikungunya: young age and inefficient type-I interferon signaling are risk factors for severe disease. |
| title_full |
A mouse model for Chikungunya: young age and inefficient type-I interferon signaling are risk factors for severe disease. |
| title_fullStr |
A mouse model for Chikungunya: young age and inefficient type-I interferon signaling are risk factors for severe disease. |
| title_full_unstemmed |
A mouse model for Chikungunya: young age and inefficient type-I interferon signaling are risk factors for severe disease. |
| title_sort |
mouse model for chikungunya: young age and inefficient type-i interferon signaling are risk factors for severe disease. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2008 |
| url |
https://doaj.org/article/1e32b6aa498f4cd1b776c683169198b3 |
| work_keys_str_mv |
AT theresecouderc amousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT fabricechretien amousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT clementineschilte amousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT olivierdisson amousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT madlybrigitte amousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT florenceguivelbenhassine amousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT yasminatouret amousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT georgesbarau amousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT nadegecayet amousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT isabelleschuffenecker amousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT philippedespres amousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT fernandoarenzanaseisdedos amousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT alainmichault amousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT matthewlalbert amousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT marclecuit amousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT theresecouderc mousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT fabricechretien mousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT clementineschilte mousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT olivierdisson mousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT madlybrigitte mousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT florenceguivelbenhassine mousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT yasminatouret mousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT georgesbarau mousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT nadegecayet mousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT isabelleschuffenecker mousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT philippedespres mousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT fernandoarenzanaseisdedos mousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT alainmichault mousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT matthewlalbert mousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease AT marclecuit mousemodelforchikungunyayoungageandinefficienttypeiinterferonsignalingareriskfactorsforseveredisease |
| _version_ |
1718414446981808128 |