JVI Accepts, published online ahead of print on 4 November 2009

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Mansuroglu, Z. Articles by Bonnefoy, E. PubMed PubMed Citation Articles by Mansuroglu, Z. Articles by Bonnefoy, E.

 Previous Article  |  Next Article 

J. Virol. doi:10.1128/JVI.01165-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Non structural NSs protein of Rift Valley Fever Virus interacts with pericentromeric DNA sequences of the host cell inducing chromosome cohesion and segregation defects

Z. Mansuroglu, T. Josse, J. Gilleron, A. Billecocq, P. Leger, M. Bouloy^*, and E. Bonnefoy^*

Régulation de la Transcription et Maladies Génétiques, CNRS UPR2228, Université Paris Descartes, 45 rue des Saints Pères, 75270, Paris cedex 06, France; Physiopathologie du contrôle de la prolifération germinale, INSERM S895, Université Paris Descartes, 45 rue des Saints Pères, 75270, Paris cedex06, France; Unité de Génétique Moléculaire des Bunyavirus, Institut Pasteur, 25 rue du Docteur Roux 75015, Paris, France

^* To whom correspondence should be addressed. Email: michele.bouloy{at}pasteur.fr. bonnefoy{at}biomedicale.univ-paris5.fr.

Rift Valley Fever Virus (RVFV) is an emerging, highly pathogenic virus whose infection can lead to encephalitis, retinitis or fatal hepatitis associated with hemorrhagic fever in humans as well as death, abortions and fetal deformities in animals. RVFV nonstructural NSs protein, a major factor of virulence, forms filamentous structures in nuclei of infected cells. In order to further understand RVFV pathology, we have investigated here the capacity of NSs to interact with the host genome using chromatin immunoprecipitation, immunofluorescence, fluorescent in situ hybridization and confocal microscopy. Our results demonstrate that even though cellular DNA is predominantly excluded from NSs filaments, NSs interacts with some specific DNA regions of the host genome such as clusters of pericentromeric -satellite sequence. Targeting of these sequences by NSs was correlated with the induction of chromosome cohesion and segregation defects in RVFV-infected murine as well as sheep cells. Using recombinant non-pathogenic virus rZHNSs210-230, expressing a NSs protein deleted of its region of interaction with cellular factor SAP30, we showed that the NSs/SAP30 interaction was essential for NSs to target pericentromeric sequences as well as for induction of chromosome segregation defects. RVFV effect upon inheritance of genetic information, is discussed with respect to the pathology associated with fetal deformities and abortions, highlighting the main role played by cellular cofactor SAP30 on the establishment of NSs interactions with host DNA sequences and RVFV pathogenesis.