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Searched keyword : Lassa virus
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Lassa virus (LASV) is an arenavirus causing hemorrhagic fever in human. 300 000 to 500 000 cases of LASV infection are reported every year in western Africa, including 5 000 to 6 000 deaths. LASV is highly pathogenic, and no vaccine or treatment is available in endemic areas. LASV pathogenesis mechanisms are not well documented, and further investigations are needed to understand viral and immunological factors involved during infection. As previously shown by studies conducted on patients and non-human primates infected by LASV, T-cell response and type I interferon (IFN-I) are important for an effective response to LASV infection. Among dendritic cells (DC), myeloid DC can induce T-cell activation and plasmacytoid DC are specialized in IFN-I response. DC are also the first target of LASV during the infection of a new host, and studies on in vitro differentiated DC suggest a role of DC in T-cell response to LASV infection. Therefore, plasmacytoid and myeloid DC could be important for an efficient response to LASV infection.
Development of a bioinformatics workflow dedicated to the analysis of the viral metagenome: from NGS raw data to the identification of novel viruses
The aim of this project is to implement, at the level of the research units, a bioinformatics workflow dedicated to the analysis of the microbiome, and of the virome in particular, based on Next Generation Sequencing (NGS) data (Illumina technology). This workflow will be applied in different contexts, from the identification of nucleotide sequences belonging to a novel or emerging pathogen (mainly viruses) presente in a clinical sample (such as serum or cerebrospinal fluid), to the determination of the whole sequence genome of isolated and uncharacterized viruses (such as bacteriophages of Leptospira).
Study of the early pathogenesis during Lassa fever in cynomolgus monkeys and its correlation with the outcome
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.