|Molecular Genetics of RNA Viruses - URA3015 CNRS, Université Paris Diderot, Paris 7|
|HEAD||Prof. van der WERF Sylvie / firstname.lastname@example.org|
|MEMBERS||Dr G. ABOU JAOUDE/ M. ANSELME-VATIN Alex / Mlle BENASSAYA Mathilde / Mme BLUMEN Brigitte / M BRIAND David / Mme CAMPANARO Malika / Dr COHEN Lisette / Dr CRESCENZO-CHAIGNE Bernadette / Mme CUVELIER Frédérique / Mlle DENIS Claire / Dr ENOUF Vincent / Dr ESCRIOU Nicolas / Mme FILLODEAU Anne-Marie / Mlle V. GRANDHOMME/ M. GROULT Guillaume/ M. HERVÉ Pierre-Louis / Mme LAGANIER Sylvie / M. LE GAL Sébastien / Melle LORIN Valérie / Mlle MARNATA Caroline / Dr MARTIN Annette / Mlle MOISY Dorothée / Dr Sandie MUNIER / Dr NAFFAKH Nadia / Dr NOULIN Nicolas / M POULAIN Damien Mme ROCA Vanessa / Dr SAULNIER Aure / Dr Dominique ROUSSET/ Mlle TOURDES Audrey
Our activities on influenza viruses (IVs), SARS coronavirus (SARS-CoV), hepatitis C virus (HCV) and GB virus B (GBV-B), include studies of the molecular evolution, expression and replication of the viral genomes, particle morphogenesis, analysis of virus host interactions and evaluation of vaccines and antiviral candidates.
Evolution of influenza viruses. Surveillance activities of human IVs by the National Influenza Center (Northern France), were focused on the pandemic H1N1 2009 virus. The impact of genetic variations of the neuraminidase (NA) of seasonal and pandemic H1N1 viruses and H5N1 viruses on the enzymatic characteristics of the NA were further studied and their cross-reactive antigenic properties were determined. The global pattern of avian IVs circulation in waterbirds in the Camargue area was further analyzed with emphasis on low pathogenic H9 and H5 viruses (coll M. Gauthier-Clerc, Tour du Valat, F. Renaud, IRD/CNRS Montpellier).
Signals at the extremities of genomic IV segments. Investigating further the possibility to exchange the non-conserved non-coding sequences of type A and C IVs viral RNAs by reverse genetics we observed that type specific determinants vary between segments.
Host range determinants of avian/human influenza viruses. Candidate host factors interacting with the polymerase complex have been identified by yeast double-hybrid (coll Y. Jacob, P.O. Vidalain, IP Paris) or by phage-display (coll. J.L. Jestin, IP Paris). Their functional relevance for virus replication and host-range is being analyzed further, using biochemical and imaging approaches. Analysis of a genetically engineered waterfowl IV with an NA stalk deletion showed enhanced viral replication and increased virulence in chickens (coll. D. Marc INRA Tours, P. Quéré, INRATours, Y. Cherel, ENV Nantes B. Labrosse, INSERM, Paris).
SARS-CoV and IV H5N1 vaccine candidates. Evaluating the immunogenicity of soluble forms of the spike protein (Ssol) of SARS-CoV or of the IV H5N1 glycoproteins a protective role of the NA was found. Protective immune responses induced by recombinant viral vectors expressing the S protein of SARS-CoV or the H5 of H5N1 were further studied in hamsters and mice, respectively (coll. P. Marianneau, UBIVE, Lyon, P. Charneau - M. Huerre – F. Tangy, IP Paris).
Hepacivirus (HCV, GBV-B) replication. Using both HCV and the closely-related, primate hepatotropic virus GBV-B in cell culture systems and primate model, we identified molecular determinants and interactions between 5' and 3' genomic nontranslated sequences and nonstructural protein NS5A involved in genome replication and virus assembly (coll. R.E Lanford, SFBR, S.M. Lemon, UTMB, USA). Our current research addresses mechanisms of hepacivirus morphogenesis using functional and structural approaches, with a focus on the role and specificity of viral nonstructural proteins in this process.
Keywords: Influenza, respiratory viruses, vaccine, polymerase, host factors, evolution, antivirals, hepatitis, replication, hepacivirus, assembly
Buchy P, Fourment M, Mardy S, Sorn S, Holl D, Ly S, Vong S, Enouf V, Peiris JS, van der Werf S. (2009) Molecular epidemiology of clade 1 influenza A viruses (H5N1), southern indochina peninsula, 2004-2007. Emerg Infect Dis. 2009 Oct;15(10):1641-4.
L. Warter*, L. Cohen*, Y. Benureau, D. Chavez, Y. Yang, F. Bodola, S.M. Lemon, C. Traboni, R.E. Lanford and A. Martin (2009). A cooperative interaction between nontranslated RNA sequences and NS5A protein promotes in vivo fitness of a chimeric hepatitis C/GB-B virus. PLoS One. 2009;4(2):e4419. Epub 2009 Feb 10.
Rameix-Welti MA., Tomoiu A., Dos Santos Afonso E., van der Werf S., Naffakh N. (2009) Avian Influenza A virus polymerase association with nucleoprotein, but not polymerase assembly, is impaired in human cells during the course of infection. J Virol. Feb;83(3):1320-31. Epub 2008 Nov 19.
Rameix-Welti MA., Enouf V., Cuvelier F., Jeannin P., van der Werf S.. (2008) Enzymatic Properties of the Neuraminidase of seasonal H1N1 Influenza Viruses provide Insights for the Emergence of Natural Resistance to Oseltamivir PLoS Pathogens Jul 25;4(7):e1000103
Callendret B., V. Lorin, P. Charneau, P. Marianneau, H. Contamin, J-M. Betton, S. van der Werf and N. Escriou. (2007) Heterologous viral RNA export elements improve expression of severe acute respiratory syndrome (SARS) coronavirus spike protein and protective efficacy of DNA vaccines against SARS. Virology 5;363(2):288-302.
Activity Reports 2009 - Institut Pasteur
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