Objective RNA viruses have the highest mutation frequencies in nature, which are in large part attributed to the low fidelity of their viral RNA-dependent RNA polymerases (RdRp). Explosive replication kinetics coupled with high mutation rates quickly generate highly diverse populations (quasispecies) maintained by mutation-selection balance. RNA virus quasispecies have been observed for nearly all RNA viruses, but whether genetic heterogeneity is a function or consequence of a the virus’ interaction with its host environment has been difficult to answer, particularly in vivo. Recently, we have developed a model system to study these questions by altering the RdRp fidelity of poliovirus, thereby changing the amount of genetic diversity present in a population. We showed that viral infectivity, dissemination and pathogenicity were dependent on the level of genetic diversity present within a viral population. We also showed that restricting genetic diversity strongly attenuates virus and may constitute a novel strategy to engineer live virus vaccines. However, the poliovirus model of infection of transgenic mice presents significant differences and limitations with respects to a natural host infection. To further extend our preliminary results, we are shifting the expertise acquired in these recent studies to a more natural model of infection, using the Coxsackie B3 virus. This new model of study will permit a more detailed determination of the role of genetic diversity in pathogenesis and a more realistic evaluation of modulating genetic diversity as a vaccine approach. Fields of science medical and health scienceshealth sciencesinfectious diseasesRNA virusescoronaviruses Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2009-RG - Marie Curie Action: "Reintegration Grants" Call for proposal FP7-PEOPLE-IRG-2008 See other projects for this call Funding Scheme MC-IRG - International Re-integration Grants (IRG) Coordinator INSTITUT PASTEUR EU contribution € 100 000,00 Address RUE DU DOCTEUR ROUX 25-28 75724 Paris France See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Administrative Contact Marco Vignuzzi (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
