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A postdoctoral position*, funded by the Laboratory of Excellence Integrative Biology of Emerging Infectious Diseases (LabEx IBEID: http://www.pasteur.fr/labex/ibeid), is available in the "Biology of Infection" research unit directed by Marc Lecuit at the Institut Pasteur in Paris.
Pathogenesis of enterovirus 71, a human emerging encephalitogenic virus ?
Enterovirus 71 (EV71) is a human emerging virus closely related to poliovirus. EV71 has a worldwide distribution that is currently expending, and is a major cause of encephalitis associated with significant mortality in Asia. It causes a benign disease, hand, foot, and mouth disease (HFMD), and frequently lethal encephalitis, in particular in young children. In summer 2012, the emergence of EV71 in Cambodia led teams of Institut Pasteur of Phnom Penh, Shanghai and Paris to put together a task force. We have since worked on the identification of viral and host factors responsible of severe and fatal disease.
EV71 isolates from benign HFMD and from fatal encephalitis have been sequenced and mouse models for the disease have been developed. All isolates are closely related and differ from each other by a small number of nucleotides. We have characterized a genetically modified mouse model susceptible to EV71 infection in which a differential susceptibility to HFMD and encephalitis isolates is observed. We will use this model to map the viral determinants responsible for severe disease, and investigate their role in EV71 replication and cell and tissue tropisms. We have also shown that weaning mice of a genetically modified mouse strain are resistant to EV71 infection, in contrast to weaning wild-type mice of the same genetic background. We will investigate in this animal model the immune components that account for the increased severity of human EV71 infection in children. Finally, we will develop and characterize humanized transgenic mice expressing the two known human-specific EV71 receptors (SCARB-2 and PSGL-1) and will use them to study further viral and host factors implicated in human EV71 infection and pathophysiology.
This project will improve the understanding of the molecular bases of EV71 virulence and of the host factors involved in EV71-associated disease, in particular those implicated in disease severity in children.
These findings will also constitute a basis from which develop antiviral strategies against EV71, and tackle a major public health threat for both developing and developed countries.
Candidate requirements: PhD, virology or cell biology. Applicants should ideally possess skills in virology, molecular biology and cell biology. Experiments on mice and mouse tissues would be appreciated.
Applicants should be highly motivated and show an ability to work within a team.
To apply: Applicants should send their CV, a motivation letter and 3 references to Therese Couderc (firstname.lastname@example.org) Biology of Infection Unit, Institut Pasteur, Inserm 1117, 28 rue du Dr Roux 75015 Paris