Molecular Genetics of Bunyaviruses  


  HEADBOULOY Michèle / mbouloy@pasteur.fr
  MEMBERSALEXANDRE Jocelyne/ BILLECOCQ Agnès Dr /BLOT Guillaume Dr /CARNEC Xavier Dr/ COUDRIER Daniel/ FAILLOUX-MANUELLAN Anna-Bella Dr/ FLAMAND Marie Dr
LARA Estelle/ LEGER Psylvia/ MARTIN Estelle/ MILLIOT Brigitte/ MOUSSON Laurence/ MOUTALLIER Sara Dr/ TAMIETTI Carole/ VAZEILLE Marie Dr


  Annual Report

The Bunyaviridae family is one of the largest taxonomic group which includes pathogens causing hemorrhagic fevers, such as Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus, Hantaan and Sin Nombre viruses.

RVFV is transmitted by mosquitoes and causes disastrous outbreaks for humans and ruminants in Africa and recently in Middle East. The Unité de Génétique Moléculaire des Bunyavirus has developed several axis of research focusing mainly on Rift Valley fever virus (RVFV) with the aim to understand the mechanisms involved in pathogenesis in vertebrates, to produce RVFV vaccines and to determine why infection of mosquitoes is asymptomatic.

Virulence, attenuation and host pathogen interactions. The nonstructural protein NSs encoded by the small segment of the tripartite RNA genome was shown to be a major determinant of virulence. To understand better RVFV pathogenesis, we identified the cellular partners of NSs. We showed that NSs inhibits Pol I- and Pol II- dependent cellular transcription by interacting with and sequestering p44, a component of the general transcription factor TFIIH. It interacts also with SAP30 a subunit of repression complexes and maintains the interferon beta gene promoter in a repressed state, preventing the production of the antiviral cellular response.

Production of attenuated vaccine candidates and reverse genetics. RVFV Clone 13 was cloned from a natural isolate as a virus deficient for NSs which contains a large internal deletion in NSs ORF. Being shown to be avirulent in the mouse model, this virus is retained as a possible vaccine candidate and is now under vaccination trials with ruminants. To manipulate the viral genes within the full length genome, a reverse genetics methodology has been established, enabling rescue of infectious viruses.

RVFV infection in mosquitoes

The virus has been isolated from more than 30 mosquito species. This low specificity ensures that RVFV is likely to become an important zoonotic disease worldwide. Experimental transmission assays are essential to assess vector competence. In an attempt to study RVFV transmission in its arthropod vector and further, to estimate the consequence of RVFV infection on life history traits of potential vectors, we have developed an artificial feeding system.

In addition to these activities, we also developed collaborations with other laboratories and Instituts Pasteur of the network, including one on chickungunya virus during La Reunion outbreak.

Keywords: arbovirus, pathogenesis, virus-host interactions, mosquito, vectorial competence

Gmbun.jpg

The NSs protein forms a nuclear filament where NSs colocalizes with subunits p44 and XPB of TFIIH as shown by immunofluorescence. (HM:high magnification). Le May et al 2004.



  Publications

LE MAY N., S. DUBAELE, L. PROETTI DE SANTIS, A. BILLECOCQ, M. BOULOY and JM EGLY. 2004. TFIIH transcription factor, a target for the Rift Valley hemorrhagic fever virus. Cell 116 (4) 541-550.

Billecocq A., M. Spiegel, P. Vialat, A. Kohl, F. Weber, M. Bouloy, and O. Haller. 2004. NSs protein of Rift Valley fever virus blocks interferon production by inhibiting host gene transcription. J Virol 78 p 9798-9806

Le May N., N. Gauliard, A. Billecocq and M. Bouloy. 2005 The N terminus of Rift Valley fever virus nucleoprotein is essential for dimerisation. J Virol. 79 p.11974-11980

N. Gauliard, A. Billecocq, R. Flick and M. Bouloy. 2006. Rift Valley fever virus noncoding regions of L, M and S segments regulate RNA synthesis. Virology 351, 170-179.

Vazeille M, Moutailler S, Coudrier D, Rousseaux C, Khun H, Huerre M, Thiria J, Dehecq JS, Fontenille D, Schuffenecker I, Despres P, and Failloux AB. 2007. Two Chikungunya Isolates from the Outbreak of La Reunion (Indian Ocean) Exhibit Different Patterns of Infection in the Mosquito, Aedes albopictus. PLoS ONE 2(11): e1168. doi:10.1371/journal.pone.0001168.





Activity Reports 2007 - Institut Pasteur
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