Lyssavirus dynamics and host adaptation  


  HEADBOURHY Hervé / hbourhy@pasteur.fr
  MEMBERSCAMPANARO Malika / COZETTE Pascal / Dr DACHEUX Laurent / Dr DELMAS Olivier / Dr GHOLAMI Alireza / LAVENIR Rachelle / LARROUS Florence / LEPELLETIER Anthony/ LUCO Sophie/ MARTIN Edith / 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 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 parts. 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 2008, we have analysed the temporal dynamics of European bat Lyssavirus type 1 in natural bat colonies and the spatiotemporal spreading of dog rabies virus, specialy 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. 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 2008, the Unit developed and validated several laboratory methods for rabies diagnosis.

Keywords: Rabies virus, phylogeny, evolution, pathogenesis



  Publications

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

Delmas O, Holmes EC, Talbi C, Larrous F, Dacheux L, Bouchier C, Bourhy H. 2008. Genomic diversity and evolution of the lyssaviruses. PLoS ONE. 2008 Apr 30;3(4):e2057. PMID: 18446239.

Bourhy H, Reynes JM, Dunham EJ, Dacheux L, Larrous F, Huong VT, Xu G, Yan J, Miranda ME, Holmes EC. 2008. The origin and phylogeography of dog rabies virus. J Gen Virol. 2008 Nov;89(Pt 11):2673-81. PMID: 18931062.

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. 2008 Dec 1;47(11):1410-7. PMID: 18937576.

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. 2008 Dec;4(12):e1000251. Epub 2008 Dec 26. PMID: 19112510.





Activity Reports 2009 - Institut Pasteur
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