Role and contribution
The emergence and re-emergence of new viral pathogens occurs periodically due to lack of control measures, changes in the ecosystems, or changes in the transmission of the disease, particularly the crossing of the species barrier. This is also true for viruses causing rabies. New variants of lyssavirus adapted to wild life species, in particular bat lyssaviruses, are causing public health problems. Furthermore, the situation of rabies in the world is not improving as expected. In many developing countries a resurgence of the disease is noticed due to a lack of concern of public health authorities. In this context, the main objective of the unit “Lyssavirus dynamics and host adaptation”is to study the biology and ecology of lyssavirus-host relationships. To reach this goal, the unit gather researchers and collaborations with complementary expertises. This association creates 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 provide us with the opportunity to understand the logic of molecular networks involved in the patho-biological process of lyssavirus infection. The research project is also intimately connected with public health problems of interest for the National Reference Centre for Rabies (NCR-Rabies) and for the World Health Organization Collaborative Center for Research and Reference for Rabies (WHOCC-Rabies) that are housed in the unit.
The sequencing and structural informations on the replicative machinery of rhabdoviruses is until now relatively scarce, although these data could be of primary importance to understand adaptation to different hosts and to develop antiviral startegies. In the framework of VIZIER, we propose to collect the largest possible amount of sequencing and structural information on the replicative machinery of lyssaviruses. This study is based on a wide collection of rhabdovirus obtained in the laboratory, from which a panel of rhabdovirus (n=15) that represents the genetic diversity of virus of medical (human and veterinary) interest within this family was selected. The full length genomic sequence or the partial sequence involved in the replicative machinery is under characterization in our lab. The virus components of the replicative machinery are being tentatively identified and the domain structure of the multidomain component predicted by other partners involved in bioinformatics. Using these predictive data, cDNAs of the regions of interest are produced in order to provide the partners involved in protein expression with entry clones.
I Pasteur Paris, FR
