期刊
COMMUNICATIONS BIOLOGY
卷 4, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s42003-020-01543-7
关键词
-
资金
- Delegation Generale pour l'Armement (Agence Nationale de la Recherche - Accompagnement Specifique des Travaux de Recherches et d'Innovation Defense, ANR-ASTRID 2014, France)
- Fondation pour la Recherche Medicale (FRM, France)
- Direction Generale de l'Armement (France) [2014015]
This study used a cynomolgus monkey model to replicate Lassa virus and associated Lassa fever, finding that in fatal cases of the disease there is a decrease in T-cell responses leading to systemic viral dissemination and multiorgan failure. The results suggest that the outcome of Lassa fever may be determined early after infection, which could help in the development of early diagnostic tools.
Lassa virus (LASV) is endemic in West Africa and induces a viral hemorrhagic fever (VHF) with up to 30% lethality among clinical cases. The mechanisms involved in control of Lassa fever or, in contrast, the ensuing catastrophic illness and death are poorly understood. We used the cynomolgus monkey model to reproduce the human disease with asymptomatic to mild or fatal disease. After initial replication at the inoculation site, LASV reached the secondary lymphoid organs. LASV did not spread further in nonfatal disease and was rapidly controlled by balanced innate and T-cell responses. Systemic viral dissemination occurred during severe disease. Massive replication, a cytokine/chemokine storm, defective T-cell responses, and multiorgan failure were observed. Clinical, biological, immunological, and transcriptomic parameters resembled those observed during septic-shock syndrome, suggesting that similar pathogenesis is induced during Lassa fever. The outcome appears to be determined early, as differentially expressed genes in PBMCs were associated with fatal and non-fatal Lassa fever outcome very early after infection. These results provide a full characterization and important insights into Lassa fever pathogenesis and could help to develop early diagnostic tools. Baillet et al. use the cynomolgus monkey model to model Lassa virus and associated Lassa fever (LF). They provide a full characterisation of LF pathogenesis with the aim of assisting the development of early diagnostic tools.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据