Unit: Lyssavirus dynamics and host adaptation
Director: BOURHY Hervé
Rabies is an acute, progressive, incurable viral encephalitis. The causative agents are neurotropic viruses in the genus Lyssavirus. Rabies is an anthropozoonosis which incidence is estimated to be 40-50,000 cases in humans annually. The main objective of the unit is to study the relationships between genomic evolution in lyssaviruses and host response to infection keeping in mind the context of crossing the species barriers, and the consequences in terms of dynamic of lyssavirus infection in the different human and animal populations. The unit also housed the National Reference Centre for Rabies and the World Health Collaborating Centre for Reference and Research on Rabies.
The main objective of this unit created on 1st November 2005 is to study the biology and ecology of lyssavirus-host relationships. The specific questions addressed are:
1. Determination of ecological and virological factors involved in the dynamics of lyssavirus infection in animal populations and in crossing the species barriers.
- Temporal dynamic of bat lyssavirus and role of the different bat species in Europe.
- Temporal and spatial dynamic of lyssavirus in North-Africa.
- Relationships between virus evolution and adaptation to understand which evolutionary events are involved in host specificity.
2. Host cells - lyssavirus interplay and virulence.
- Identification of transcriptional/translational modification(s) playing a pivotal role in determining a given disease phenotype.
- Role of the matrix protein in the range of early genetic response of the neuronal cells to successful (in the case of pathogenic viruses) and abortive (in the case of less pathogenic viruses) infections.
- Drawing of a tentative map of the complex "interactome" of lyssavirus proteins with cellular partners and study the role of the genetic diversity of lyssaviruses in the modulation of these interactions.
To reach this goal, the unit will gather researchers and collaborations with complementary expertises. This work will be based on:
- collection of field data, modelisation of dynamic of population, phylogenetic analysis and sequence analysis for virological and ecological studies,
- micro-array analysis and reverse proteomics for exploring the comparative molecular pathogenesis of lyssavirus infections of neurones.
This association will create a multidisciplinary environment that approaches the study of lyssavirus and host interplay from the level of dynamics of infection into the host population to the molecular mechanisms conditioning the early response of the cells to lyssavirus infection and the virulence of lyssaviruses in a new host species. The "integrative" approaches proposed in the present project will also provide us with the opportunity to understand the logic of molecular networks involved in the patho-biological process of lyssavirus infection.
National Reference Center for Rabies (NRC-Rabies) (Laurent dacheux, Laurent Audry, Patrick Weber, Florence Larrous, Pascal Cozette, Edith Martin, Malika Campanaro and Hervé Bourhy in collaboration with Maryvonne Goudal, Yolande Rotivel, Department of Clinical Research)
The NRC-Rabies is involved in the control of human rabies in France. It is responsible for the laboratory diagnosis of every suspected human case (10 suspicions in 2005) and of any animal that could possibly have transmitted rabies to humans (1536 analyses in total in 2005). Metropolitan France has been free of rabies in non-flying animals since April 2001. However the number of cases of rabies developing in France that have been acquired outside French territory is increasingly posing new epidemiological problems. In addition, new variants of lyssaviruses adapted to bats have been identified in France, and in Europe as a whole. These new epidemiological developments reinforce the need to maintain the survey and control of rabies. We are currently working, in collaboration with other relevant public health institutions, on the measures of prevention to be proposed to bat handlers.
World Health Collaborating Centre for Reference and Research on Rabies (WHOCC Rabies) (Laurent Dacheux, Laurent Audry, Patrick Weber, Florence Larrous, Pascal Cozette, Edith Martin, Malika Campanaro and Hervé Bourhy)
During 2004, the WHOCC Rabies participated in the training of 3 scientists in laboratory diagnosis and rabies control methods, in the molecular characterization of isolates sent by foreign collaborating institutes and in strengthening rabies surveillance and prevention in Asia particularly. Furthermore, a multicentric collaborative study involving the network of Pasteur Institutes (in Senegal, Cambodia and Madagascar) to define protocols of intra-vitam rabies diagnosis is currently taking place. A rabies workshop has been organized in Shanghai with WHO, Shanghai CDC and Institut Pasteur of Shanghai, Chinease Academy of Sciences.
Keywords: Virology, Epidemiology, Ecosystems, Encephalitis, Rabies, Lyssavirus, Dynamic, Host