Results

At only halfway the project’s duration, using the generated knowledge and insights of the studies performed thus far under the three fiels of expertise, VECTORIE managed to develop several vaccine candidates against WNV and CHIKV using two different state-of-the-art technology platforms for the production of vaccines. These vaccine candidates will now be tested for their protective capacity against WNV and CHIKV infection, and will be compared using the preclinical read-out systems that have been developed within this project.

At the end of 2013, it is expected that the generated knowledge and insights within VECTORIE have allowed for the development of a surveillance system and response plan appropriate for European countries to detect, predict and deal with emerging WNV and CHIKV outbreaks. In addition, the studies will lead to novel knowledge that will enable Europe to improve its ability to monitor the spread of these infections inEurope, and will lead to diagnostic and prognostic tools as well as novel strategies to treat infected patients. Finally, VECTORIE addressesEurope’s need for novel vaccine strategies for these vector-borne diseases, since an efficient approach to control outbreaks caused by WNV and CKIKV is vaccination of people at risk.

Publications

Lim, Koraka, Osterhaus, Martina. West NileVirus: Immunity and Pathogenesis. Viruses 2011, 3: 811-828
Abstract Viruses 2011

Kremer, Suezer, Volz, Frenz, Majzoub, Hanschmann, Lehmann, Kalinke, Sutter. Critical role of perforin-dependent CD8+ T Cell immunity for rapid protective vaccination in a murine model for human smallpox. PLoS Pathogens 2012, 8(3).
Abstract PloS Path 2012

Fros, J. J., Domeradzka, N. E., Baggen, J, Geertsema, C, Flipse, J, Vlak, J. M. & Pijlman, G. P. (2012). Chikungunya virus nsP3 blocks stress granule assembly by recruitment of G3BP into cytoplasmic foci. J Virol 86, 10873-10879. http://jvi.asm.org/content/86/19/10873.long

Chikungunya virus nonstructural protein nsP3 has an essential but unknown role in alphavirus replication and interacts with Ras-GAP SH3 domain-binding protein (G3BP). Here we describe the first known function of nsP3, to inhibit stress granule assembly by recruiting G3BP into cytoplasmic foci. A conserved SH3 domain-binding motif in nsP3 is essential for both nsP3-G3BP interactions and viral RNA replication. This study reveals a novel role for nsP3 as a regulator of the cellular stress response.

Chikungunya Virus nsP3 Blocks Stress Granule Assembly by Recruitment of G3BP into Cytoplasmic Foci Jelke J. Fros, Natalia E. Domeradzka, Jim Baggen, Corinne Geertsema, Jacky Flipse, Just M. Vlak and Gorben P. Pijlman. Abstract

Cellular pathways altered following West Nile virus infection in mouse model using in-gel and off-gel quantitative proteomic analysis. Christophe Fraisier, Luc Camoin, Stéphanie Lim, Mahfoud Bakli, Maya Belghazi, Patrick Fourquet, Samuel Granjeaud, A.D.M.E. Osterhaus, Penelope Koraka, Byron Martina and Lionel Almeras. Abstract

Presentations

11th Arbovirus Research in Australia Symposium, 9-14 September 2012, Surfer’s Paradise, Australia. Gorben P Pijlman. Chikungunya virus nsP2 and nsP3 differentially antagonize host responses.

31st Annual Meeting of the American Society for Virology, 21-25 July 2012, Madison-Wisconsin, USA. Gorben P. Pijlman, Jim Baggen, Corinne Geertsema, Natalia Domeradzka, Jacky C. Flipse, Just M. Vlak. Chikungunya virus nsP3 interaction with mammalian G3BP and mosquito Rasputin in cytoplasmic granules.

31st Annual Meeting of the American Society for Virology, 21-25 July 2012, Madison-Wisconsin, USA. Jelke J. Fros, Corinne Geertsema, Erika van der Maten, Hetty Manenschijn, Just M. Vlak & Gorben P.  Pijlman. The C-terminus of chikungunya virus nsP2 determines inhibition of interferon-induced JAK-STAT signaling, replication and cytopathicity.

22nd Annual Meeting of the Society for Virology, 14–17 March 2012, Essen, Germany.Jelke J. Fros, Corinne Geertsema, Esther Schnettler, Just M. Vlak & Gorben P.  Pijlman. Chikungunya virus nonstructural protein 2 is a potent inhibitor of  type I/II interferon-stimulated JAK-STAT signaling.

22nd Annual Meeting of the German Society for Virology
14-17 March 2012, Essen, Germany Kaserer, Fichte, Sutter. Recombinant vaccinia MVA as West Nile Virus vaccines for VECTORIE. Abstract