Lyssavirus dynamics and host adaptation  


  HEADDr BOURHY Hervé / herve.bourhy@pasteur.fr
  MEMBERSCOZETTE Pascal / Dr DACHEUX Laurent / Dr DELMAS Olivier / LAVENIR Rachel / LARROUS Florence / LEPELLETIER Anthony/ LUCO Sophie/ MARTIN Edith / MBOW Awa / TALBI Chiraz


  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 Unit ‘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 parts.

The first part 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 2009, we have analysed the spatio-temporal spreading of dog rabies virus, western and central in Africa.

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. The role of the viral proteins and in particular the matrix protein and the phosphoprotein is also studied in details. 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 on these proteins should result in a better understanding of the basic molecular mechanisms involved in lyssavirus adaptation and pathogenesis for humans. In 2009, the three dimensional structure of these 2 proteins were obtained allowing us to describe important domains in the regulation of the virus biological life cycle.

To reach this goal, the unit gathers 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 (www.vizier-europe.org and www.rabmedcontrol.org) in which we were 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 Centre for Research and Reference for Rabies that are housed in the unit. In 2009, the Unit developed and validated several laboratory methods for rabies diagnosis.

Keywords: Rabies virus, phylogeny, evolution, pathogenesis, epidemiology



  Publications

Dacheux L, Larrous F, Mailles A, Boisseleau D, Delmas O, Biron C, Bouchier C, Capek I, Muller M, Ilari F, Lefranc T, Raffi F, Goudal M, Bourhy H. European bat Lyssavirus transmission among cats, Europe. 2009. Emerg. Infect. Dis. 15(2):280-4. PMID: 19193273.

Talbi C, Holmes EC, de Benedictis P, Faye O, Nakouné E, Gamatié D, Diarra A, Elmamy BO, Sow A, Adjogoua EV, Sangare O, Dundon WG, Capua I, Sall AA, Bourhy H. 2009 Apr. Evolutionary history and dynamics of dog rabies virus in western and central Africa. J. Gen. Virol. 90(Pt 4):783-91. PMID: 19264663.

Graham SC, Assenberg R, Delmas O, Verma A, Gholami A, Talbi C, Owens RJ, Stuart DI, Grimes JM, Bourhy H. 2008. Rhabdovirus matrix protein structures reveal a novel mode of self-association. PLoS Pathog. 4(12):e1000251. PMID: 19112510.

Dacheux L, Reynes JM, Buchy P, Sivuth O, Diop BM, Rousset D, Rathat C, Jolly N, Dufourcq JB, Nareth C, Diop S, Iehlé C, Rajerison R, Sadorge C, Bourhy H. 2008. A reliable diagnosis of human rabies based on analysis of skin biopsy specimens. Clin. Infect. Dis. 47(11):1410-7. PMID: 18937576.

Gholami A., Kassis R, Real E, Delmas O., Guadagnini S., Larrous F., Obach D., Prevost MC, Jacob Y, Bourhy H. 2008. Mitochondrial dysfunction in lyssavirus-induced apoptosis. J. Virol. 82(10):4774-84. PMID: 18321977.





Activity Reports 2009 - Institut Pasteur
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