Molecular Genetics of Bunyaviruses


  HEADDr BOULOY Michèle / mbouloy@pasteur.fr
  MEMBERSDr BILLECOCQ Agnès / Dr BLOT Guillaume / Dr CARNEC Xavier
Dr FAILLOUX-MANUELLAN Anna-Bella / LARA Estelle / LEGER Psylvia
MOUTALLIER Sara


  Annual Report

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

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 Bunyaviridés has developed several axes 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. Recently, 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. Through this interaction NSs acts as a strong antagonist of the antiviral cellular response which blocks drastically the interferon beta 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. This virus being shown to be avirulent for the very sensitive mouse model, it is retained as a possible vaccine candidate and it is under vaccination trials in ruminants. To manipulate the viral genes within the full-length genome, a Pol I- based 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 lack of specificity ensures that RVFV is likely to become an important zoonotic disease worldwide. Transmission experiments 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 research activities, the Unité has also specific collaboration with other laboratories (CNR arbovirus and Institut Pasteur in Iran, Tunisia, Madagascar and Senegal).

bouloy.jpg

Fig 1. La protéine NSs forme un filament nucléaire où NSs colocalise avec des sous-unités p44 et XPB de TFIIH comme montré par immunofluorescence. (HM:high magnification). Le May et al 2004.

Fig 1. 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

Publications 2006 of the unit on Pasteur's references database




Activity Reports 2006 - Institut Pasteur
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