A Mouse Model for Chikungunya: Young Age and Inefficient Type-I Interferon Signaling Are Risk Factors for Severe Disease
By T. Couderc, F. Chrétien, C. Schilte, Olivier Disson, M. Brigitte, F. Guivel-Benhassine, Y. Touret, G. Barau, N. Cayet, I. Schuffenecker and 5 more. PLoS Pathogens, 2008
641 citations recorded by the source corpus.
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-α/βR+/−) or totally (IFN-α/βR−/−) 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.
Subfields: Infectious Diseases, Public Health, Environmental and Occupational Health, Virology
View Paper: https://www.semanticscholar.org/paper/feb1b6ce017921ccbc787682b8c1d87a43724c0a
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Infectious Diseases
Citations in the corpus
- Biology and pathogenesis of chikungunya virus (2010, background): “Following transmission, CHIKV replicates in the skin and then disseminates to the liver and joints, presumably through the bloo”
- Persistent Chronic Inflammation and Infection by Chikungunya Arthritogenic Alphavirus in Spite of a Robust Host Immune Response (2010, background): “Alphavirus infections, including CHIKV, rapidly induce IFNa/b production (31, 32).”
- Severe Acute Respiratory Syndrome Coronavirus Infection Causes Neuronal Death in the Absence of Encephalitis in Mice Transgenic for Human ACE2 (2008, background): “However, we could not detect viral antigen anywhere in the gut of two infected mice (data not shown), raising the possibility that once virus is established in the brain, it spreads along specific neurotransmitter pathways (such as the serotoninergic dorsal raphe system) that innervate large portion”
- Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System? (2019, background): “For example, the rabies virus [77], herpes simplex and other herpes viruses (HHV) [72,78–81], arthropod-borne flaviviruses such as the West Nile virus (WNV), Japanese encephalitis virus (JEV), chikungunya virus (CHIKV), Zika virus (ZIKV), alphaviruses such as the Venezuelan, Western and Eastern equi”