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Project #7820
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#7820 : Study of the early pathogenesis during Lassa fever in cynomolgus monkeys and its correlation with the outcome
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Name of Applicant : Sylvain Baize
Date of application : 02-02-2017
Unit : Biology of Viral Emerging Infections
Location : Lyon
Phone : +33437282443
@ Mail : sylvain.baize@pasteur.fr

Project context and summary :

Because of their increasing incidence, dramatic severity, lack of treatment or vaccine, complicated diagnosis, misreading of the pathogenesis, and need for a maximum containment, Viral Hemorrhagic Fevers (VHF) constitute a major public health problem. There is therefore an urgent need to further study VHF to understand the pathogenesis of the severe disease and the host responses involved in their control or in the dramatic damages. Among VHF, Lassa fever (LF) is probably the most worrying one because of its endemicity and the large number of cases. LF is caused by the Old-World arenavirus Lassa virus (LASV). It is endemic to West Africa and is responsible for 300,000 cases and 5,000 to 6,000 deaths each year. We propose here to study the pathogenesis of VHF by using LF in cynomolgus monkeys as a paradigm, with a particular emphasis on the very early events. The viral tropism, pathophysiological mechanisms, and immune responses will be studied during the course of infection, including the incubation period. Powerful approaches will be used to (1) identify early biological markers of infection, to be able to confirm infection and isolate patients; (2) determine the viral tropism and dynamics during the course of infection to understand the natural history of virus into its host. (3) characterize the early pathogenic events that lead to the severe hemorrhagic syndrome to fully understand the pathophysiogenesis of VHF and identify new therapeutic targets. (4) identify the immune responses involved in the control of infection or in the fatal outcome, to reveal the involvement of immunopathological mechanisms and help to design a vaccine approach. This ambitious and unprecedented project will allow to develop therapeutic and prophylactic approaches but also to identify early biological markers of infection and improve the early diagnosis to optimize the management of outbreaks in the field and increase the survival rate in patients.


Related team publications :
Pannetier D, S Reynard, M Russier, X Carnec and S Baize. 2014. Production of CXC and CC chemokines by human antigen-presenting cells in response to Lassa virus or closely related immunogenic viruses, and in cynomolgus monkeys with Lassa fever. PLoS Neglected Tropical Diseases. 8:e2637
Pannetier D, M Russier, S Reynard, A Journeaux, N Tordo, V Deubel, and S Baize. 2011. Human dendritic cells infected with the non-pathogenic Mopeia virus induce stronger T-cell responses than with Lassa virus. Journal of Virology. 85:8293-306
Baize S, Marianneau P, Loth P, Reynard S, Journeaux A, Chevallier M, Tordo N, Deubel V, and H Contamin. 2009. Early and strong immune responses are associated with control of viral replication and recovery in Lassa virus-infected cynomolgus monkeys. Journal of Virology. 83: 5890-5903
Service Delivery
Project Manager : emeline.perthame@pasteur.fr
Project Type : Long
Status : In Progress


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