1. TFIIH Transcription Factor, a Target for the Rift Valley Hemorrhagic Fever Virus
- Author
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Luca Proietti De Santis, Nicolas Le May, Jean-Marc Egly, Michèle Bouloy, Agnès Billecocq, Sandy Dubaele, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique Moléculaire des Bunyavirus, Institut Pasteur [Paris] (IP), This work was supported by grants from Pasteur Institute to M.B. and from the CNRS, INSERM, ULP, and the Commissariat à l'Energie Atomique (laboratoire correspondant), the Association pour la Recherche sur le Cancer (ARC9083) and EEC (QLG1-1999 and QLRT-1999-02002) as well as the EEC Descartes Award to J.M.E. N.L.M. is a recipient of a fellowship from the Ministère de la Recherche, S.D. received BDI/CNRS, La ligue contre le cancer and Fondation pour la Recherche Médicale fellowships and L.P.S. from INSERM., This work is the result of an equal contribution between our two laboratories. We thank Daniel Christmann (Hospices Civils de Strasbourg), Joseph P. Dougherthy (Piscataway (NJ, US), Jean-Pierre Liautard (Montpellier), and Geoffrey Richards (Strasbourg) for fruitful discussions and critical reading of the manuscript. Thanks are also due to Jean Luc Vonesh for help and advice for confocal experiments, Yves Jacob for setting up the two-hybrid system, and to Isabelle Kolb and Jean Luc Weickert for baculovirus assays., and Institut Pasteur [Paris]
- Subjects
Time Factors ,Transcription, Genetic ,MESH: Plasmids/metabolism ,MESH: Microscopy, Fluorescence ,Plasma protein binding ,Mice ,Transcription Factors, TFII ,MESH: Transcription Factors, TFII/chemistry ,Plasmid ,MESH: Microscopy, Confocal ,MESH: Animals ,MESH: DNA, Complementary/metabolism ,Luciferases ,0303 health sciences ,Microscopy, Confocal ,MESH: Transcription Factor TFIIH ,MESH: Rift Valley fever virus/metabolism ,MESH: RNA/metabolism ,3. Good health ,MESH: Luciferases/metabolism ,MESH: Cell Nucleus/metabolism ,medicine.anatomical_structure ,MESH: Transcription Factors, TFII/metabolism ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Transcription factor II H ,Plasmids ,Protein Binding ,DNA, Complementary ,Protein subunit ,Two-hybrid screening ,Biology ,MESH: Two-Hybrid System Techniques ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Two-Hybrid System Techniques ,MESH: Gene Library ,medicine ,Animals ,Humans ,MESH: Protein Binding ,MESH: Mice ,Gene Library ,030304 developmental biology ,Cell Nucleus ,MESH: Humans ,Biochemistry, Genetics and Molecular Biology(all) ,030306 microbiology ,MESH: Transcription, Genetic ,MESH: Time Factors ,RNA ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,Rift Valley fever virus ,MESH: Cell Nucleus/virology ,Virology ,Cell nucleus ,Transcription Factor TFIIH ,Microscopy, Fluorescence ,MESH: HeLa Cells ,HeLa Cells - Abstract
International audience; The Rift Valley fever virus (RVFV) is the causative agent of fatal hemorrhagic fever in humans and acute hepatitis in ruminants. We found that infection by RVFV leads to a rapid and drastic suppression of host cellular RNA synthesis that parallels a decrease of the TFIIH transcription factor cellular concentration. Using yeast two hybrid system, recombinant technology, and confocal microscopy, we further demonstrated that the nonstructural viral NSs protein interacts with the p44 component of TFIIH to form nuclear filamentous structures that also contain XPB subunit of TFIIH. By competing with XPD, the natural partner of p44 within TFIIH, and sequestering p44 and XPB subunits, NSs prevents the assembly of TFIIH subunits, thus destabilizing the normal host cell life. These observations shed light on the mechanism utilized by RVFV to evade the host response.
- Published
- 2004
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