Partner 1: P1

Participating organisation: Institut Pasteur, Paris, France
Research laboratory: Rabies Laboratory
Principal Scientist: Dr Hervé Bourhy
Other Scientists: Dr Laurent Dacheux, Dr M.Goudal

Role and contribution:

• To develop and participate to the validation of diagnostic tools for lyssaviruses

• To co-ordinate the selection and the shipment of positive specimens for molecular studies

• To perform necropsy of dead bats and collection of different tissues for RNA extraction

• To perform serology, immunofluorescence and RT-PCR studies on bat samples collected in Tunisia and Morocco

• To sequence the nucleoprotein and glycoprotein genes of bat lyssavirus

• To perform sequencing of genes coding for cytochrome-b and NADH dehydrogenase subunit 2 from different bat species to estimate the gene flow

• To co-ordinate the workpackage 5 (Molecular epidemiology of lyssavirus isolates).

• To amplify by RT-PCR animal and human lyssavirus isolates obtained from Egypt and Algeria

• To perform phylogenetic analysis of nucleotide sequences obtained during the WP5 and available from the databanks using a maximum likelihood approach and different models of sequence evolution

• To identify specific nucleotide sites on lyssavirus sequences showing positive selection and correlating with animal species specificity

• To predict the function of these mutations through computer prediction and simulation

The Institut Pasteur has a very long and historical contribution in the control of rabies in the world through the discovery of the vaccine by Louis Pasteur and through the development of the network of Pasteur Institutes around the world. The Rabies Laboratory (11 people) in Institut Pasteur is mandated at national level to perform rabies diagnosis and surveillance in humans and animals. It is the Reference Centre for rabies for the french Ministry of Health. The Rabies Laboratory is also a WHO Collaborative Center for Reference and Research on Rabies. It has extensive experience and knowledge in epidemiology, diagnosis of lyssavirus infections, molecular biology/virology and phylogenetic analysis.The Rabies Laboratory has a large number of collaborations with European and North African laboratories working on rabies. One of the research subject of the rabies unit is to investigate the mechanisms of genetic variation and adaptation of lyssaviruses and to understand at the molecular level the mechanisms controling the crossing of the species barrier by the virus. This work lead to the characterization of the different genotypes of lyssaviruses, of the different phylogenetic lineages within each genotypes, and of selective pressures during the natural evolution of lyssaviruses. Strong genetic constraints limiting the evolution of non synonymous changes were evidenced. Several studies of the rabies unit in collaboration with other institutes have also described the natural infection of bats by European bat lyssaviruses. The Rabies Laboratory has already established cooperations with 5 of the 6 Partners of this project.

F. Larrous and L. Audry have over 15 years of technical experience in molecular biology and rabies. L. Dacheux, Pharmacist, PhD, is an expert in virology and molecular biology. H. Bourhy, DVM, PhD, HDR is the head of the Rabies Laboratory, director of the National Reference Centre for Rabies for the Ministry of Health and Director of the WHO Collaborative Centre for Rabies. He has over 15 years of experience in molecular virology and diagnosis of lyssaviruses. M. Goudal, DM, is in charge of the Rabies treatment center at the Pasteur Institute. She is an expert in patient management at the National Reference Centre for Rabies.

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