Lyssavirus dynamics and host adaptation  


  HEADDr BOURHY Hervé / hbourhy@pasteur.fr
  MEMBERSDr AMENGUAL Blanca / AUDRY Laurent / CAMPANARO Malika / COZETTE Pascal / Dr DACHEUX Laurent / Dr DELMAS Olivier
GHOLAMI Alireza / LAVENIR Rachelle / LARROUS Florence / MARTIN Edith / TALBI Chiraz / WEBER Patrick


  Annual Report

Rabies is an acute, progressive, incurable viral encephalitis. The causative agents are neurotropic RNA viruses in the family Rhabdoviridae, genus Lyssavirus. Rabies is an anthropozoonosis that affects many different animal species and which has an epidemiology that changes with time. The main objective of UPRE ‘Lyssavirus dynamics and host adaptation’ is to study the relationships between genomic evolution in lyssaviruses and host response to infection, and the consequences in terms of dynamic of lyssavirus infection in the different human and animal populations. It is divided into 2 main work packages.

The first deals with the determination of the ecological and virological factors involved in the dynamics of lyssavirus infection in animal populations (dogs and bats). It is based on ecological, epidemiological and viral genetic studies which together help to explain how a lyssavirus spreads or maintains itself in a target animal species.

In particular in 2007, we have analysed the temporal dynamics of European bat Lyssavirus type 1 and the survival of Myotis myotis bats in natural colonies.

The second part presents an analysis of the host cell and virus interplay at the molecular level and its relations with the crossing of the species barrier. Mechanisms associated with the rapid induction of a programmed neuronal cell death after infection and that could be associated with a lower pathogenesis were characterized in the laboratory. The elucidation of the range of early response of the neuronal cells to successful (in the case of pathogenic viruses) and abortive (in the case of less pathogenic viruses) infections helps to reveal which transcriptional/translational modification(s) play(s) a pivotal role in determining a given disease phenotype. The role of the viral proteins and in particular the matrix protein in the regulation of host cell expression and activation of apoptosis is also studied in more details. This part is based on high throughput transcriptome screening techniques (DNA microarray technology) and proteomics screening techniques. The elucidation of the critical points of the early phase of lyssavirus infection together with the identification and the localization of the potential viral and cellular determinants of virulence should result in a better understanding of the basic molecular mechanisms involved in lyssavirus adaptation and pathogenesis for humans.

To reach this goal, the unit gather researchers and collaborations with complementary expertise. Briefly, these are with our colleagues from the Departments of “Infection and Epidemiology” and “Virology”, from the technological platforms in Pasteur Institute, from other institutes of the International Network of Pasteur Institutes, particularly those located in Africa and in Asia where the burden of rabies is the highest and with all those participating to FP6 funded projects (VIZIER and RABMEDCONTROL) in which we are involved. The research project is also intimately connected with public health problems of interest for the National Reference Centre for Rabies and for the World Health Organization Collaborative Center for Research and Reference for Rabies that are housed in the unit. In 2007, the Unit developped and validated several laboratory methods for rabies diagnosis.

Keywords: Rabies virus, phylogeny, evolution, pathogenesis



  Publications

Amengual B, Bourhy H, López-Roig M, Serra-Cobo J. 2007. Temporal dynamics of European bat Lyssavirus type 1 and survival of Myotis myotis bats in natural colonies. PLoS ONE. Jun 27;2(6):e566. PMID: 17593965.

Feyssaguet M, Dacheux L, Audry L, Compoint A, Morize JL, Blanchard I, Bourhy H. 2007. Multicenter comparative study of a new ELISA, PLATELIA RABIES II, for the detection and titration of anti-rabies glycoprotein antibodies and comparison with the rapid fluorescent focus inhibition test (RFFIT) on human samples from vaccinated and non-vaccinated people. Vaccine. Mar 8;25(12):2244-51. PMID: 17224214.

Davis PL, Holmes EC, Larrous F, Van der Poel WH, Tjørnehøj K, Alonso WJ, Bourhy H. 2005. Phylogeography, population dynamics, and molecular evolution of European bat lyssaviruses. J Virol. Aug;79(16):10487-97. PMID: 16051841.

Reynes JM, Molia S, Audry L, Hout S, Ngin S, Walston J, Bourhy H. 2004. Serologic evidence of lyssavirus infection in bats, Cambodia. Emerg Infect Dis. 2004 Dec;10(12):2231-4. PMID: 15663870.

Kassis R, Larrous F, Estaquier J, Bourhy H. 2004. Lyssavirus matrix protein induces apoptosis by a TRAIL-dependent mechanism involving caspase-8 activation. J Virol. 2004 Jun;78(12):6543-55. PMID: 15163747.





Activity Reports 2007 - Institut Pasteur
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